Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) i... | NCT02622724

ID	Type	Description	Link
2014-005260-15	EudraCT Number

Status Module

Name	Class
Seventh Framework Programme	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FP-1201-lyo 10 μg	Experimental	FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.	Drug: Interferon beta-1a
FP-1201-lyo Placebo	Placebo Comparator	FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Interferon beta-1a	Drug	Investigational drug	FP-1201-lyo 10 μg	FP-1201-lyo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28	VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).	Day 28

Secondary Outcomes

Measure	Description	Time Frame
Efficacy Endpoint: All-cause Mortality	Fatalities, mortality all-causes from randomisation up to Day 28	At Day 28
Efficacy Endpoint: Mortality in ICU	All-cause mortality for subjects who died in Intensive Care Units up to Day 28.

Other Outcomes

Measure	Description	Time Frame
Evaluation of Safety: Vital Signs - Heart Rate	Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point. No statistical analyses were made for vital signs.	From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

All patients must be intubated and mechanically ventilated to diagnose ARDS and be eligible for the study

Patient has a diagnosis of moderate or severe ARDS according to the Berlin definition of ARDS:
- Acute onset of respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms
- Respiratory failure associated with known ARDS risk factors and not fully explained by either cardiac failure or fluid overload (an objective assessment of cardiac failure or fluid overload is needed if no risk factors for ARDS [moderate or severe ARDS] are present)
- Radiological abnormalities on chest X-ray or on computerised tomography scan, i.e., bilateral opacities that are not fully explained by effusions, nodules, masses or lobar/lung collapse
- Hypoxaemia:
  - Moderate ARDS: PaO2/FiO2 >100 mmHg (>13.3 kPa) to ≤200 mmHg (≤26.6 kPa) with positive end expiratory pressure (PEEP) ≥5 cmH2O
  - Severe ARDS: PaO2/FiO2 ≤100 mmHg (≤13.3 kPa) with positive end expiratory pressure [PEEP] ≥5 centimeter of water [cmH2O]
The radiological and hypoxaemia criteria (1.3 and 1.4) must be met within the same 24-hour period. The time of onset of ARDS is when the last of the two specified ARDS criteria is met
Administration of the first dose of study drug must be planned to take place within 48 hours of moderate or severe ARDS diagnosis
Patient is intubated and mechanically ventilated
A signed informed consent form from the patient or the patient's personal legal representative or a professional legal representative must be available
Patient is aged ≥18 years

Exclusion Criteria:

Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
Patient is simultaneously taking part in another pharmacotherapy protocol
Patient is not expected to survive for 24 hours
Patient has an underlying clinical condition where, in the opinion of the Investigator, it would be extremely unlikely that the patient would come off ventilation, e.g., motor neurone disease, Duchenne muscular dystrophy or rapidly progressive interstitial pulmonary fibrosis
Patient has severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for continuous positive airway pressure (CPAP) or bi-level positive airway pressure used solely for sleep-disordered breathing
Patient has congestive heart failure, defined as New York Heart Association class IV
Patient has acute left ventricular failure
Patient has liver failure (Child-Pugh grade C)
Patient has received any prior interferon
Patient has known hypersensitivity to natural or recombinant IFN beta or to any of the excipients
Patient is receiving renal dialysis therapy for chronic renal failure
Patient is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
Patient has had any form of mechanical ventilation (invasive or non-invasive, excluding CPAP alone) for longer than 48 hours prior to the diagnosis of ARDS. Non-invasive ventilation has to be continuously applied for at least 12 hours per day in these 48 hours
Patient has burns to ≥15% of their total body surface area

Name	Affiliation	Role
Geoffrey Bellingan, MD	University College London Hospitals, NHS, London, UK	Study Director
V Marco Ranieri, Prof. MD	Universita La Sapeinza Policlinico Umberto I, Rome, Italy	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Erasmus Hospital		Brussels		B-1070	Belgium
UZ Brussel

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36927455	Derived	Jalkanen J, Khan S, Elima K, Huttunen T, Wang N, Hollmen M, Elo LL, Jalkanen S. Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19. Crit Care. 2023 Mar 16;27(1):112. doi: 10.1186/s13054-023-04388-8.
32065831	Derived	Ranieri VM, Pettila V, Karvonen MK, Jalkanen J, Nightingale P, Brealey D, Mancebo J, Ferrer R, Mercat A, Patroniti N, Quintel M, Vincent JL, Okkonen M, Meziani F, Bellani G, MacCallum N, Creteur J, Kluge S, Artigas-Raventos A, Maksimow M, Piippo I, Elima K, Jalkanen S, Jalkanen M, Bellingan G; INTEREST Study Group. Effect of Intravenous Interferon beta-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2020 Feb 25;323(8):725-733. doi: 10.1001/jama.2019.22525.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon beta-1a: Investigational drug
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 29, 2017	Aug 28, 2019

Arm/Group Information

ID	Title	Description
BG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon beta-1a: Investigational drug
BG001	Placebo	Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28

VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).

Full Analysis Set (FAS), 296 subjects.

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon beta-1a: Investigational drug
OG001	Placebo	Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug

Units	Counts
Participants	OG000144 OG001152

Title

Denominators

Categories

Title	Measurements
	OG00010(-1 to 26) OG0018.5(-1 to 26)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A non-parametric analysis has been used as the data distribution was skewed. This involved a generalised Wilcoxon rank sum-based stratification test which assigns ranks within strata and compares two treatments within strata (Van Elteren hypothesis test).	Van Elteren hypothesis test		0.8219														Superiority

Secondary

Efficacy Endpoint: All-cause Mortality

Fatalities, mortality all-causes from randomisation up to Day 28

Full Analysis Set (FAS) defined as all randomised subjects that received atleast one dose of study drug.

Posted

Number

95% Confidence Interval

percentage of subjects

At Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Efficacy Endpoint: Mortality in ICU

All-cause mortality for subjects who died in Intensive Care Units up to Day 28.

Full Analysis Set

Posted

Number

95% Confidence Interval

percentage of subjects

Up to Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Efficacy Endpoint: Mortality in Hospital

This is the number of subjects who died in hospital (i.e. outside of Intensive Care Units) up to Day 28.

Full Analysis Set

Posted

Count of Participants

Participants

Up to Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoints: Days Free of Organ Failure

The total number of days free of organ failure by Sequential Organ Failure Assessment (SOFA) methodology. Overall, the median number of days free of organ failure was 0 days in both the treatment groups.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoints: Days Free of Renal Support

Days without renal support (any renal support was documented). Overall, the median number of days free of renal support was 28 days in the active group and 27 days in the placebo group.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support

Days without vasoactive support. The vasoactive support included catecholamine and non-catecholamine vasopressors, inotropes and vasodilating agents.

Overall, the median number of days free of vasoactive support was 20 days in the active group and 21 days in the placebo group.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation

The total number of days free of mechanical ventilation has been derived from the Patient Status report recorded on each day during the 28-day period. Patients who died during this period have been assigned a value of zero. This variable differs from the calculated "Ventilation Free Days (VFD) endpoint, which contribute to the VDFsurv primary efficacy endpoint as it require additional conditions of unassisted breathing (UAB) to be met.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoints: Number of ICU-free Days

Number of Intensive Care Unit free days up to Day 28, i.e. the patient is no longer receiving care in ICU. Patients who die during this period have been assigned a value of zero for the number of ICU care free days.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Other Secondary Efficacy Endpoints: Number of Days in Hospital

Hospitalisation days (including the stay at Intensive Care Units). Patients who died during this period have been assigned a value of 28 for the number of days in ICU or in hospital.

Full Analysis Set

Posted

Median

Full Range

Days

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Evaluation of Safety: Adverse Events and Deaths

Adverse events (AE) up to Day 28. Per protocol, AEs occurring after Day 28 if the investigator considered a causal relationship with the study drug as well as all deaths up to Day 360 were reported. Treatment-emergent AEs (TEAEs) were defined as AEs that begins or worsens in intensity after at least one dose of study drug has been administered. Serious AEs (SAEs) were defined as any untoward medical occurrence that at any dose resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was an important medical event.

The analysis population included all participants who were randomized and received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

AEs up to Day 28, only related after Day 28 and deaths up to Day 360

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants

Secondary

Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a

The immunological response to FP-1201-lyo was assessed by monitoring presence of anti-drug binding antibodies (BAbs) and neutralising antibodies (NAbs) to IFN beta-1a on pre-dose Day 1 and at Day 28, the last day in ICU or early termination (if earlier). The BAbs were determined first, and if present, the NAbs were also determined. Presence of BAbs and NAbs were summarised categorically, using positive/negative classification.

Full Analysis Set, the subjects who had laboratory evaluation done. Subjects were analysed for IFN beta NAbs only if BAbs were present.

Posted

Count of Participants

Participants

Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants

Secondary

Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker

Evaluation of MxA biomarker change from baseline to D14 between treatments arms over time.

Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Posted

Mean

Standard Deviation

ng/ml

From baseline to Day 14

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Units	Counts
Participants	OG000

Secondary

Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180

Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to long term follow-up (Day 180 visit).

Subjects from Full Analysis Set population who completed QoL questionnaire at Baseline and Day 180.

Posted

Median

Full Range

change score on a scale

Change from baseline to Day 180

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1)

Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity.

Full Analysis Set

Posted

Mean

Standard Deviation

%FEV1

Day 180

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Secondary

Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT)

The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % conf.interval) for the overall treatment difference was analysed.

All subjects in Full Analysis Set population who performed atleast one 6MWT test at Day 180 visit. Furthest distance walked during the two tests was analysed using an ANOVA model.

Posted

Mean

Standard Deviation

maximum distance walked (meters)

Day 180

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Other Pre-specified

Evaluation of Safety: Vital Signs - Heart Rate

Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

No statistical analyses were made for vital signs.

Safety Population - no statistical analyses were made for vital signs.

Posted

Mean

Standard Deviation

bpm

From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Safety: Vital Signs - Body Temperature

No statistical analyses were made for vital signs.

Safety Population - no statistical analyses were made for vital signs.

Posted

Mean

Standard Deviation

degrees Celsius

From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Safety: Vital Signs - Blood Pressure

No statistical analyses were made for vital signs.

Safety Population - no statistical analyses were made for vital signs.

Posted

Mean

Standard Deviation

mmHg

From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Safety: Physical Examination

Physical examination data (covering the major body systems; general appearance, head [ear, nose and throat], cardiovascular, eyes, respiratory, abdomen, urogenital, musculoskeletal, neurological, lymph nodes and skin) were categorized as "normal"; "abnormal, not clinically significant;" "abnormal, clinically significant" or "not done". Physical examinations were performed at Screening, then at the Last day in ICU and Day 28 (Out of ICU) or Early Termination, from which the last observation performed is derived. The changes from baseline to the last observations performed are categorized as "no change", "change clinically significant"; "change not clinically significant", "not done".

Safety population - no statistical analyses were made

Posted

Count of Participants

Participants

From baseline to Last Observation Performed (D28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Units	Counts

Other Pre-specified

Evaluation of Safety: Laboratory Results

Laboratory safety assessments of biochemistry, haematology and urinalysis were performed daily during the stay at ICU. Laboratory data were classified according to normal ranges as out of range (OOR; not clinically significant), OOR (clinically significant), or OOR (clinically significant and an AE). Laboratory test results were summarised by actual results by baseline and last observation period.

Safety Population -no statistical analyses were made

Posted

Count of Participants

Participants

From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Days Free of Organ Failure

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected.

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Days Free of Renal Support

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected.

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Days Free of Vasoactive Support

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected.

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Days Free of Mechanical Ventilation

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Number of ICU-free Days

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Evaluation of Pharmacoeconomics: Number of Days in Hospital

Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

Costs items from hospitals were not collected.

Posted

Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90

Composite endpoint including mortality and days free of mechanical ventilation (VFDsurv) within 90 days among survivors. Ventilation Free Survival at Day 90 has been classified as Dead, Alive but on a ventilator and Alive and breathing unassisted

Full Analysis Set (discontinued not included).

Posted

Count of Participants

Participants

Within 90 days

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration

Evaluation of Cluster of differentiation 73 (CD73) change from baseline to D14 between treatments arms over time.

Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Posted

Mean

Standard Deviation

ng/ml

From baseline to Day 14

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Units	Counts
Participants	OG000

Other Pre-specified

Changes in Levels of Potential Inflammatory Markers (PIMs)

Evaluation of potential inflammatory markers (PIMs) change from baseline to D14 between treatments arms over time. Potential biomarkers included IL-1ra, IL-6, FGF basic, IP-10 and TNF-α.

Subjects from Full Analysis Set population for whom samples were available; analysis of last observation performed.

Posted

Mean

Standard Deviation

pg/mL

From baseline to Day 14

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Units	Counts
Participants	OG000

Other Pre-specified

Pharmacogenetic Analysis

An optional genetic sample was analysed for subjects based on a separate consent. A carrier frequency was analysed for a C/T polymorphism (rs9984723) located in the 3'PRIME_UTR/intron region of IFNAR2-gene, which encodes the beta chain for the IFN-alpha/beta receptor and encompasses a regulatory motif for the glucocorticoid receptor. Biomarker responders were defined by a 3-fold elevation in MxA and a 2-fold in CD73 in comparison to baseline.

Only subjects with consent for a genetic sample were analysed. Carriers of the C-allele were analysed in biomarker responders compared to biomarker non-responders. 5 and 6 subjects failed to provide genotype information in analyses for responder and non-responders, respectively.

Posted

Count of Participants

Participants

Anytime from baseline to Day 28

ID	Title	Description
OG000	Biomarker Responder	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Biomarker Non-responder	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.

Units	Counts
Participants

Other Pre-specified

Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360

Fatalities; as the study was terminated early, the assessment time point for mortality at Day 360 was not reached. Therefore only the overall mortality at study termination is presented.

Full Analysis Set, but the study was terminated early. The mortality numbers include 3 study subjects who had SAEs with an onset before the first dose of IMP and who subsequently died.

Posted

Count of Participants

Participants

Day 360 /termination of study

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Other Pre-specified

Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360

Subjects from Full Analysis Set population who completed QoL questionnaire at Baseline and Day 360. As the study was terminated early, only a limited amount of data were available at the post-baseline time point.

Posted

Median

Full Range

change score on a scale

Change from baseline to Day 360

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants

Other Pre-specified

Neurological Functioning (6MWT) at Extended Long-term Follow-up

The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % confidence intervals) for the overall treatment difference was analysed.

All subjects in Full Analysis Set population who performed atleast one 6MWT test at Day 360, before the study was early terminated.

Posted

Mean

Standard Deviation

maximal distance walked (meters)

Day 360

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days

Units

Other Pre-specified

Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360

Subjects from Full Analysis Set population attending Day 360 visit.

Posted

Mean

Standard Deviation

%FEV1

Day 360

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Post-Hoc

Post-Hoc Analyses Related to the Use of Concomitant Glucocorticoids Medications and Mortality at D28

The overall use of concomitant glucocorticoids treatment in both study treatment groups (active and placebo) were analysed.

Subjects who received at least 1 dose of concomitant glucocorticoids during days 0-28

Posted

Number

percentage of participants

Day 28

ID	Title	Description
OG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) for 6 days.
OG001	Placebo	Placebo for 6 days.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FP-1201-lyo 10 μg	FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days. Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection. Interferon beta-1a: Investigational drug	51	144	77	144	109	144
EG001	Placebo	Placebo will be administered once daily as an intravenous bolus injection for 6 days. Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection. Placebo: Placebo for investigational drug	53	152	77	152	110	152

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0019 events9 affected152 at risk
HYPOXIA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events4 affected144 at risk EG0016 events6 affected152 at risk
ACUTE RESPIRATORY DISTRESS SYNDROME	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0017 events7 affected152 at risk
LARYNGEAL OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0013 events3 affected152 at risk
PNEUMOMEDIASTINUM	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
PNEUMOTHORAX	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0013 events3 affected152 at risk
ACUTE PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
HAEMOPTYSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
PULMONARY FIBROSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
RESPIRATORY DISTRESS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ASPIRATION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CHRONIC RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA ASPIRATION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PULMONARY THROMBOSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RESPIRATORY TRACT CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
MULTI-ORGAN FAILURE	General disorders	MedDRA (21.0)	Systematic Assessment	EG00013 events13 affected144 at risk EG0018 events8 affected152 at risk
CONDITION AGGRAVATED	General disorders	MedDRA (21.0)	Systematic Assessment	EG0007 events7 affected144 at risk EG00112 events11 affected152 at risk
DISEASE PROGRESSION	General disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0011 events1 affected152 at risk
DEATH	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ASTHENIA	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BRAIN DEATH	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CHILLS	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GENERAL PHYSICAL HEALTH DETERIORATION	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PYREXIA	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0005 events5 affected144 at risk EG0019 events9 affected152 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0007 events7 affected144 at risk EG0015 events5 affected152 at risk
SEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0014 events4 affected152 at risk
BACTERAEMIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
EMPYEMA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
DISSEMINATED TUBERCULOSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HERPES ZOSTER MENINGOENCEPHALITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LUNG ABSCESS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
MENINGITIS ASPERGILLUS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
NEUTROPENIC SEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PERITONITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA INFLUENZAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PNEUMONIA PSEUDOMONAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SYSTEMIC CANDIDA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
UROSEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SHOCK HAEMORRHAGIC	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0006 events6 affected144 at risk EG0012 events2 affected152 at risk
SHOCK	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0014 events4 affected152 at risk
HYPERTENSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0010 events0 affected152 at risk
HYPOTENSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPOVOLAEMIC SHOCK	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
THROMBOSIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CARDIAC ARREST	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0015 events5 affected152 at risk
MYOCARDIAL INFARCTION	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
BRADYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CARDIAC DISORDER	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CARDIO-RESPIRATORY ARREST	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CARDIOGENIC SHOCK	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PULSELESS ELECTRICAL ACTIVITY	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TORSADE DE POINTES	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
VENTRICULAR FIBRILLATION	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CRITICAL ILLNESS POLYNEUROPATHY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0012 events2 affected152 at risk
BASAL GANGLIA HAEMORRHAGE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BRAIN HYPOXIA	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BRAIN INJURY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CEREBRAL INFARCTION	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CEREBRAL VENOUS THROMBOSIS	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DEPRESSED LEVEL OF CONSCIOUSNESS	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EPILEPSY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HAEMORRHAGE INTRACRANIAL	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPOXIC-ISCHAEMIC ENCEPHALOPATHY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
INTRAVENTRICULAR HAEMORRHAGE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ISCHAEMIC STROKE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
QUADRIPLEGIA	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SEIZURE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
INTESTINAL ISCHAEMIA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DUODENAL ULCER HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTRITIS HAEMORRHAGIC	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTROINTESTINAL NECROSIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
INTRA-ABDOMINAL HAEMATOMA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
MELAENA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SMALL INTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
UPPER GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ACUTE MYELOID LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ADENOCARCINOMA OF THE CERVIX	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CHOLANGIOCARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
COLORECTAL CANCER METASTATIC	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DIFFUSE LARGE B-CELL LYMPHOMA RECURRENT	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LUNG ADENOCARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LUNG NEOPLASM	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LUNG NEOPLASM MALIGNANT	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
METASTASES TO KIDNEY	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
METASTASES TO LIVER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
METASTASES TO LUNG	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
NEUROENDOCRINE CARCINOMA OF THE SKIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
NON-HODGKIN'S LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SMALL CELL LUNG CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0015 events5 affected152 at risk
POST INFECTION GLOMERULONEPHRITIS	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RENAL IMPAIRMENT	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ANASTOMOTIC LEAK	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BAROTRAUMA	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DELAYED RECOVERY FROM ANAESTHESIA	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTROINTESTINAL ANASTOMOTIC COMPLICATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GASTROINTESTINAL ANASTOMOTIC LEAK	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HUMERUS FRACTURE	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
VASCULAR ACCESS COMPLICATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RENAL REPLACEMENT THERAPY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
WITHDRAWAL OF LIFE SUPPORT	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
EXTRACORPOREAL MEMBRANE OXYGENATION	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTRIC OPERATION	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LAPAROTOMY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TRANSAMINASES INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BIOPSY BONE MARROW ABNORMAL	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0010 events0 affected152 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DISSEMINATED INTRAVASCULAR COAGULATION	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HEPATIC FAILURE	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
ACUTE HEPATIC FAILURE	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ISCHAEMIC HEPATITIS	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SUBCUTANEOUS EMPHYSEMA	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CONFUSIONAL STATE	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0008 events8 affected144 at risk EG0014 events4 affected152 at risk
SEPTIC SHOCK	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events1 affected144 at risk EG0014 events3 affected152 at risk
SEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0008 events8 affected144 at risk EG0013 events3 affected152 at risk
BACTERAEMIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0015 events5 affected152 at risk
DEVICE RELATED SEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0011 events1 affected152 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0013 events3 affected152 at risk
CYTOMEGALOVIRUS INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
FUNGAL INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
LUNG ABSCESS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA PSEUDOMONAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
BRONCHITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
CANDIDA INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ENDOCARDITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
ENTEROBACTER PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
IMPETIGO	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
LUNG INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA INFLUENZAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SUPERINFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
SYSTEMIC CANDIDA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ASPERGILLUS INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BACTERIAL DISEASE CARRIER	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BRONCHOPULMONARY ASPERGILLOSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CANDIDA PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CANDIDURIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CELLULITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ENTEROCOCCAL INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EPIGLOTTITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ESCHERICHIA BACTERAEMIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
FUNGAEMIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GENITAL HERPES SIMPLEX	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HERPES SIMPLEX PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
INFECTIOUS PLEURAL EFFUSION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
INFLUENZA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LYMPHANGITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
OESOPHAGEAL CANDIDIASIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ORAL CANDIDIASIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
OTITIS EXTERNA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
OTITIS MEDIA ACUTE	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PANCREATIC ABSCESS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PNEUMOCYSTIS JIROVECII PNEUMONIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PNEUMONIA ESCHERICHIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA STAPHYLOCOCCAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PNEUMONIA VIRAL	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PULMONARY SEPSIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PYELONEPHRITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RENAL ABSCESS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SINUSITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SPUTUM PURULENT	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
STAPHYLOCOCCAL BACTERAEMIA	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
STAPHYLOCOCCAL INFECTION	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
THROMBOPHLEBITIS SEPTIC	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TINEA CRURIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
VULVOVAGINAL CANDIDIASIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
VULVOVAGINITIS	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPOXIA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events4 affected144 at risk EG0013 events3 affected152 at risk
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0011 events1 affected152 at risk
PNEUMOTHORAX	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events3 affected144 at risk EG0018 events8 affected152 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0008 events8 affected144 at risk EG0014 events4 affected152 at risk
ACUTE RESPIRATORY DISTRESS SYNDROME	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
PNEUMOMEDIASTINUM	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0013 events3 affected152 at risk
ACUTE PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
PNEUMONIA ASPIRATION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
ACUTE RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ASPIRATION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events1 affected144 at risk EG0010 events0 affected152 at risk
BRONCHOSPASM	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
HAEMOPTYSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERCAPNIA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
INCREASED BRONCHIAL SECRETION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
PULMONARY FIBROSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RESPIRATORY DISTRESS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ATELECTASIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
HAEMOTHORAX	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
INTERSTITIAL LUNG DISEASE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HICCUPS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LARYNGEAL DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
LUNG CONSOLIDATION	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
LUNG DISORDER	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PNEUMOTHORAX SPONTANEOUS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RESPIRATORY ACIDOSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RESPIRATORY ALKALOSIS	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
STRIDOR	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PYREXIA	General disorders	MedDRA (21.0)	Systematic Assessment	EG00021 events17 affected144 at risk EG00112 events12 affected152 at risk
CONDITION AGGRAVATED	General disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0015 events5 affected152 at risk
CHILLS	General disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events2 affected144 at risk EG0010 events0 affected152 at risk
GENERALISED OEDEMA	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0013 events3 affected152 at risk
HYPERTHERMIA	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
HYPOTHERMIA	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
MEDICAL DEVICE COMPLICATION	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ADVERSE DRUG REACTION	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CATHETER SITE NECROSIS	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DISEASE RECURRENCE	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DRUG WITHDRAWAL SYNDROME	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HYPERTHERMIA MALIGNANT	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PAIN	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG00012 events11 affected144 at risk EG00114 events14 affected152 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events5 affected144 at risk EG0017 events7 affected152 at risk
VOMITING	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0015 events5 affected152 at risk
IMPAIRED GASTRIC EMPTYING	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0014 events4 affected152 at risk
INTESTINAL ISCHAEMIA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
MELAENA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
DYSPHAGIA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTRIC HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
ILEUS PARALYTIC	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
RECTAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
ABDOMINAL COMPARTMENT SYNDROME	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ILEUS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
NAUSEA	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
PANCREATITIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
UPPER GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
COLITIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DUODENAL ULCER	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GASTRIC ULCER	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTRIC ULCER HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HAEMATEMESIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
MOUTH HAEMORRHAGE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
OESOPHAGITIS	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PANCREATITIS ACUTE	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
REGURGITATION	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG00011 events9 affected144 at risk EG00116 events15 affected152 at risk
TACHYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0016 events6 affected152 at risk
SUPRAVENTRICULAR TACHYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events3 affected144 at risk EG0013 events3 affected152 at risk
BRADYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0013 events3 affected152 at risk
CARDIAC DISORDER	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
ARRHYTHMIA SUPRAVENTRICULAR	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
ATRIAL FLUTTER	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
MYOCARDIAL ISCHAEMIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
VENTRICULAR TACHYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
ARRHYTHMIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ATRIAL TACHYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ATRIOVENTRICULAR BLOCK	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BUNDLE BRANCH BLOCK RIGHT	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CARDIAC FAILURE	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CARDIAC FAILURE ACUTE	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CARDIOPULMONARY FAILURE	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CYANOSIS	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PERICARDITIS	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SINUS BRADYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SINUS TACHYCARDIA	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HYPERNATRAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG00010 events9 affected144 at risk EG0017 events7 affected152 at risk
FLUID OVERLOAD	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0009 events8 affected144 at risk EG0015 events4 affected152 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events5 affected144 at risk EG0019 events6 affected152 at risk
HYPERGLYCAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0013 events3 affected152 at risk
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0014 events3 affected152 at risk
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
HYPONATRAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
METABOLIC ALKALOSIS	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0013 events3 affected152 at risk
ALKALOSIS	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
FLUID RETENTION	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
MALNUTRITION	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
FOOD INTOLERANCE	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GOUT	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERAMMONAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERTRIGLYCERIDAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPOVOLAEMIA	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
OVERWEIGHT	Metabolism and nutrition disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERTENSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG00013 events11 affected144 at risk EG00110 events10 affected152 at risk
SHOCK HAEMORRHAGIC	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
HYPOTENSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0016 events6 affected152 at risk
VENOUS THROMBOSIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0010 events0 affected152 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
THROMBOSIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CIRCULATORY COLLAPSE	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HAEMODYNAMIC INSTABILITY	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HAEMORRHAGE	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ORTHOSTATIC HYPOTENSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PERIPHERAL ISCHAEMIA	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PHLEBITIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SUBCLAVIAN VEIN THROMBOSIS	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
THROMBOPHLEBITIS SUPERFICIAL	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
VASCULAR OCCLUSION	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
VENOUS THROMBOSIS LIMB	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TRANSAMINASES INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0019 events7 affected152 at risk
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0015 events5 affected152 at risk
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0014 events4 affected152 at risk
HEPATIC ENZYME INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0013 events3 affected152 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BLOOD CHLORIDE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
BLOOD LACTIC ACID INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
BLOOD POTASSIUM INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
BLOOD SODIUM INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
OXYGEN SATURATION DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
ANTICOAGULATION DRUG LEVEL INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BLOOD GLUCOSE DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BLOOD GLUCOSE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BLOOD IRON DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BLOOD LACTATE DEHYDROGENASE INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BLOOD PHOSPHORUS DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
BLOOD POTASSIUM DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BLOOD TRIGLYCERIDES INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
BLOOD UREA INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
C-REACTIVE PROTEIN INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CLOSTRIDIUM TEST POSITIVE	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EJECTION FRACTION DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ELECTROCARDIOGRAM ABNORMAL	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ELECTROENCEPHALOGRAM ABNORMAL	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EOSINOPHIL COUNT INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HAEMOGLOBIN DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
MYOGLOBIN BLOOD INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
PO2 DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RED BLOOD CELL COUNT DECREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SPLEEN SCAN ABNORMAL	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TROPONIN INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
WHITE BLOOD CELL COUNT INCREASED	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ANAEMIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG00018 events16 affected144 at risk EG00111 events11 affected152 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0007 events7 affected144 at risk EG0016 events6 affected152 at risk
THROMBOCYTOSIS	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events5 affected144 at risk EG0013 events3 affected152 at risk
COAGULOPATHY	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
LEUKOCYTOSIS	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
DISSEMINATED INTRAVASCULAR COAGULATION	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HAEMOLYSIS	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HISTIOCYTOSIS HAEMATOPHAGIC	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
MICROCYTIC ANAEMIA	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HEPATOCELLULAR INJURY	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0009 events9 affected144 at risk EG0018 events8 affected152 at risk
CHOLESTASIS	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0015 events5 affected152 at risk
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0013 events3 affected152 at risk
HEPATIC FUNCTION ABNORMAL	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0013 events3 affected152 at risk
HEPATIC FAILURE	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
ACUTE HEPATIC FAILURE	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
HEPATIC CIRRHOSIS	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HEPATORENAL SYNDROME	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HEPATOTOXICITY	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
JAUNDICE CHOLESTATIC	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
LIVER DISORDER	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
LIVER INJURY	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
AGITATION	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0007 events6 affected144 at risk EG0017 events7 affected152 at risk
DELIRIUM	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0008 events8 affected144 at risk EG0013 events3 affected152 at risk
ANXIETY	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected144 at risk EG0012 events2 affected152 at risk
INSOMNIA	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0012 events2 affected152 at risk
CONFUSIONAL STATE	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0011 events1 affected152 at risk
DEPRESSION	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
WITHDRAWAL SYNDROME	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
DISORIENTATION	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HALLUCINATION	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
NIGHTMARE	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RESTLESSNESS	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0008 events7 affected144 at risk EG0018 events8 affected152 at risk
RENAL FAILURE	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0006 events6 affected144 at risk EG0015 events5 affected152 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events1 affected152 at risk
CHRONIC KIDNEY DISEASE	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
RENAL INJURY	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
URINARY RETENTION	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
URINARY INCONTINENCE	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
CRITICAL ILLNESS POLYNEUROPATHY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected144 at risk EG0017 events7 affected152 at risk
CONFUSIONAL STATE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
EPILEPSY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
NERVOUS SYSTEM DISORDER	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
SEIZURE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CEREBROVASCULAR DISORDER	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
COMA	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HEADACHE	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYDROCEPHALUS	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
POLYNEUROPATHY	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SEDATION	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TREMOR	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
VOCAL CORD PARALYSIS	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ENDOTRACHEAL INTUBATION COMPLICATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0012 events2 affected152 at risk
ANASTOMOTIC LEAK	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
BAROTRAUMA	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
POST PROCEDURAL HAEMORRHAGE	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
TRACHEAL INJURY	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events1 affected152 at risk
ANIMAL BITE	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
EAR INJURY	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
FACE INJURY	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
FALL	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
FOREIGN BODY ASPIRATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
JOINT DISLOCATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
JOINT INJURY	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
MECHANICAL VENTILATION COMPLICATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
POST PROCEDURAL COMPLICATION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
TENDON RUPTURE	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
TRANSFUSION REACTION	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
WOUND HAEMATOMA	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events2 affected144 at risk EG0013 events3 affected152 at risk
DECUBITUS ULCER	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0013 events2 affected152 at risk
RASH GENERALISED	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
DERMATITIS ALLERGIC	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
URTICARIA	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
DERMATITIS CONTACT	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
ECCHYMOSIS	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PSORIASIS	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SKIN DISCOLOURATION	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SKIN NECROSIS	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
SKIN ULCER	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0005 events5 affected144 at risk EG0011 events1 affected152 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0011 events1 affected152 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
MIXED CONNECTIVE TISSUE DISEASE	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
MYOPATHY	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
RHEUMATOID ARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
SYSTEMIC LUPUS ERYTHEMATOSUS	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
RENAL REPLACEMENT THERAPY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0012 events2 affected152 at risk
ENDOTRACHEAL INTUBATION	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0012 events2 affected152 at risk
EXTRACORPOREAL MEMBRANE OXYGENATION	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
GASTRECTOMY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
GASTROSTOMY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
TRACHEOSTOMY	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
KAPOSI'S SARCOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
CONJUNCTIVAL OEDEMA	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected144 at risk EG0010 events0 affected152 at risk
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
DIPLOPIA	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
DRY EYE	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
EYE DISORDER	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
PUPILS UNEQUAL	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
ULCERATIVE KERATITIS	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk
HYPERTROPHIC CARDIOMYOPATHY	Congenital, familial and genetic disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
TINNITUS	Ear and labyrinth disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected144 at risk EG0010 events0 affected152 at risk
HYPERTHYROIDISM	Endocrine disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected144 at risk EG0011 events1 affected152 at risk

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D012120	Respiration Disorders

ID	Term
D016899	Interferon-beta
D007370	Interferon Type I
D007372	Interferons
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors

ID	Term
D012128	Respiratory Distress Syndrome
D012131	Respiratory Insufficiency