A Study in Participants With Acute Major Bleeding to Eval... | NCT02329327

Status Module

Name	Class
Portola Pharmaceuticals, LLC (a wholly owned subsidiary of Alexion Pharmaceuticals)	INDUSTRY
Population Health Research Institute	OTHER

Label	Type	Description	Intervention Names
Andexanet	Experimental	Participants received andexanet as an intravenous bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.	Biological: Andexanet

Name	Type	Description	Arm Group Labels	Other Names
Andexanet	Biological	There were 2 possible dosing regimens: Low dose = 400 milligram (mg) bolus plus 4 mg/minute continuous infusion for 120 minutes; High dose = 800 mg bolus plus 8 mg/minute continuous infusion for 120 minutes.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline In Anti-fXa Activity By FXa Inhibitor	Anti-fXa activity was measured to assess the ability of andexanet to reverse the anticoagulant effect of FXa inhibitors. Baseline was defined as the last value obtained prior to the start of the andexanet bolus. The change from baseline was calculated as the reduction in anti-fXa activity from baseline to the on-treatment nadir (that is, the minimum value between end of bolus and end of infusion). Percent reduction was calculated as the ratio between the maximum change from baseline and the baseline value, multiplied by 100.	Baseline, 12 Hours (post infusion)
Participants Achieving Hemostatic Efficacy	Hemostatic efficacy was achieved when the body had time to produce thrombin and a subsequent clot and was rated by the EAC as: excellent; good; poor/none; not evaluable due to non-administrative reasons; not evaluable due to administrative reasons. These ratings were based on pre-specified criteria that were included in the EAC Charter. The EAC was blinded to anti-fXa activity levels. Participant results were classified as either success or failure based on the hemostatic efficacy rating (success = excellent/good, failure = poor/none). Participants rated by the EAC as non-evaluable due to administrative reasons were excluded from the analysis of hemostatic efficacy.	12 Hours (post infusion)

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline In Anti-fXa Activity By Hemostatic Efficacy	This outcome measure assessed the relationship between hemostatic efficacy and anti-fXa activity in participants receiving an FXa inhibitor who had acute major bleeding. Anti-fXa activity was measured to assess the ability of andexanet to reverse the anticoagulant effect of FXa inhibitors. Baseline was defined as the last value obtained prior to the start of the andexanet bolus. Hemostatic efficacy was achieved when the body had time to produce thrombin and a subsequent clot and was rated by the EAC as: excellent; good; poor/none; not evaluable due to non-administrative reasons; not evaluable due to administrative reasons.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Acute major bleeding episode that required urgent reversal of anticoagulation; defined by at least one of the following:
- Acute bleeding that was potentially life-threatening, or
- Acute bleeding associated with a fall in hemoglobin level by ≥2 grams/deciliter (g/dL), or
- Acute bleeding associated with a hemoglobin level of ≤8 g/dL if no baseline hemoglobin was available, or
- Acute bleeding in a critical area or organ such as intraspinal, pericardial, or intracranial.
If bleeding was intracranial or intraspinal, the participant must have undergone a head computed tomography (CT) or magnetic resonance imaging (MRI) scan demonstrating the bleeding.
Participant received or was believed to have received one of the following within 18 hours prior to andexanet administration: apixaban, rivaroxaban, edoxaban, or enoxaparin.
For participants with intracranial bleeding, there must be a reasonable expectation that andexanet treatment will commence within 2 hours of the baseline imaging evaluation.

Key Exclusion Criteria:

The participant was scheduled to undergo surgery in less than 12 hours, with the exception of minimally invasive surgery/procedures.
Participant with an intracerebral hemorrhage that had any of the following:
- Glasgow coma score <7, or
- Intracerebral hematoma >60 cubic centimeters as assessed by CT or MRI
Participants with visible, musculoskeletal or intra-articular bleeding as their qualifying bleed.
Expected survival of less than 1 month.
Recent history (within 2 weeks) of a diagnosed thrombotic event as follows: venous thromboembolism, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris hospitalization or severe peripheral vascular disease within 2 weeks prior to Screening.
Severe sepsis or septic shock at the time of Screening.
Pregnant or a lactating female.
Participant received any of the following drugs or blood products within 7 days of Screening:
- Vitamin K antagonist
- Dabigatran
- Prothrombin Complex Concentrate (PCC) products or recombinant factor VIIa (rfVIIa)
- Whole blood, plasma fractions
Treated with an investigational drug <30 days prior to Screening.
Planned administration of PCC, fresh frozen plasma or rfVIIa from Screening until within 12 hours after the end of the andexanet infusion.

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Study Site		Long Beach	California		United States
Clinical Study Site

PubMed Identifier	Type	Citation	Retractions
27573206	Result	Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M; ANNEXA-4 Investigators. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016 Sep 22;375(12):1131-41. doi: 10.1056/NEJMoa1607887. Epub 2016 Aug 30.
28009495

Label	URL
Neurocrit Care. 2019;31:S37	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Andexanet	Participants received andexanet as an intravenous (IV) bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
FG001	Andexanet - Additional Participants

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	Nov 30, 2018	Oct 28, 2021

Arm/Group Information

ID	Title	Description
BG000	Andexanet	Participants received andexanet as an intravenous (IV) bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
BG001	Andexanet - Additional Participants	Two additional participants received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes. Data from these 2 participants were obtained and evaluated after the data cutoff date of 30-June-2020 and, as such, are presented separately.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00077.9± 10.66 BG00171.0± 11.31 BG00277.9± 10.66

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000218 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00016 BG0010 BG002

Race/Ethnicity, Customized

Asian participants and American Indian or Alaska Native participants are reported as Other.

Number

participants

Title

Denominators

Categories

Race : White

Title	Measurements
	BG000414 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

North America

Title	Measurements
	BG000212 BG0010 BG002

FXa Inhibitor

Count of Participants

Participants

Title

Denominators

Categories

Apixaban

Title	Measurements
	BG000245 BG0010 BG002

Bleed Type

Endpoint Adjudication Committee (EAC) determined if each participant met the bleeding entry criteria for inclusion in the Efficacy Population.

Count of Participants

Participants

Title

Denominators

Categories

Gastrointestinal

Title	Measurements
	BG000109 BG0010

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

Percent Change From Baseline In Anti-fXa Activity By FXa Inhibitor

Anti-fXa activity was measured to assess the ability of andexanet to reverse the anticoagulant effect of FXa inhibitors. Baseline was defined as the last value obtained prior to the start of the andexanet bolus. The change from baseline was calculated as the reduction in anti-fXa activity from baseline to the on-treatment nadir (that is, the minimum value between end of bolus and end of infusion). Percent reduction was calculated as the ratio between the maximum change from baseline and the baseline value, multiplied by 100.

Efficacy Population: all participants who received any amount of andexanet, met clinical bleeding criteria, and had an anti-fXa level of ≥75 nanograms/milliliter (ng/mL) for apixaban and rivaroxaban, ≥40 ng/mL for edoxaban, and ≥0.25 international units (IU)/mL for enoxaparin.

Posted

Median

95% Confidence Interval

Percent Change

Baseline, 12 Hours (post infusion)

ID	Title	Description
OG000	FXa Inhibitor: Apixaban	Participants who had recently received FXa inhibitor apixaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG001	FXa Inhibitor: Rivaroxaban	Participants who had recently received FXa inhibitor rivaroxaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG002	FXa Inhibitor: Edoxaban	Participants who had recently received FXa inhibitor edoxaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG003	FXa Inhibitor: Enoxaparin	Participants who had recently received FXa inhibitor enoxaparin received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG004	FXa Inhibitor: Rivaroxaban - Additional Participants	Two additional participants who had recently received FXa inhibitor rivaroxaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes. Data from these 2 participants were obtained and evaluated after the data cutoff date of 30-June-2020 and, as such, are presented separately.

Units	Counts
Participants	OG000169 OG001130 OG00228 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-93.3(-94.2 to -92.5) OG001-94.1(-95.1 to -93.0) OG002-71.3(-82.3 to -65.2) OG003

Primary

Participants Achieving Hemostatic Efficacy

Hemostatic efficacy was achieved when the body had time to produce thrombin and a subsequent clot and was rated by the EAC as: excellent; good; poor/none; not evaluable due to non-administrative reasons; not evaluable due to administrative reasons. These ratings were based on pre-specified criteria that were included in the EAC Charter. The EAC was blinded to anti-fXa activity levels. Participant results were classified as either success or failure based on the hemostatic efficacy rating (success = excellent/good, failure = poor/none). Participants rated by the EAC as non-evaluable due to administrative reasons were excluded from the analysis of hemostatic efficacy.

Efficacy Population: all participants who received any amount of andexanet, met clinical bleeding criteria, and had an anti-fXa level of ≥75 ng/mL for apixaban and rivaroxaban, ≥40 ng/mL for edoxaban, and ≥0.25 IU/mL for enoxaparin.

Posted

Count of Participants

Participants

12 Hours (post infusion)

ID	Title	Description
OG000	FXa Inhibitor: Apixaban	Participants who had recently received FXa inhibitor apixaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG001	FXa Inhibitor: Rivaroxaban	Participants who had recently received FXa inhibitor rivaroxaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.

Secondary

Percent Change From Baseline In Anti-fXa Activity By Hemostatic Efficacy

This outcome measure assessed the relationship between hemostatic efficacy and anti-fXa activity in participants receiving an FXa inhibitor who had acute major bleeding. Anti-fXa activity was measured to assess the ability of andexanet to reverse the anticoagulant effect of FXa inhibitors. Baseline was defined as the last value obtained prior to the start of the andexanet bolus. Hemostatic efficacy was achieved when the body had time to produce thrombin and a subsequent clot and was rated by the EAC as: excellent; good; poor/none; not evaluable due to non-administrative reasons; not evaluable due to administrative reasons.

Posted

Median

95% Confidence Interval

Percent Change

Baseline, 12 Hours (post infusion)

ID	Title	Description
OG000	FXa Inhibitor: Apixaban	Participants who had recently received FXa inhibitor apixaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.
OG001	FXa Inhibitor: Rivaroxaban	Participants who had recently received FXa inhibitor rivaroxaban received andexanet as an IV bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion administered over ~120 minutes.

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	Andexanet: Low Dose	Participants who had recently received FXa inhibitors received andexanet as an IV 400-mg bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion of 480 mg (4 mg/minute) administered over ~120 minutes.	66	382	157	382	40	382
EG001	Andexanet: High Dose	Participants who had recently received FXa inhibitors received andexanet as an IV 800- mg bolus administered over ~15 to 30 minutes, followed immediately by a continuous infusion of 960 mg (8 mg/minute) administered over ~120 minutes.	15	97	43	97	8	97

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ischaemic Stroke	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0008 events8 affected382 at risk EG0012 events2 affected97 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected382 at risk EG0014 events4 affected97 at risk
Haemorrhage Intracranial	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0007 events7 affected382 at risk EG0010 events0 affected97 at risk
Cerebral Haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0005 events5 affected382 at risk EG0010 events0 affected97 at risk
Cerebral Infarction	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0012 events2 affected97 at risk
Seizure	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected382 at risk EG0011 events1 affected97 at risk
Neurological Decompensation	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0012 events2 affected97 at risk
Intraventricular Haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected2 at risk
Brain Oedema	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
Cerebral Ischaemia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Depressed Level Of Consciousness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Intracranial Venous Sinus Thrombosis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
Transient Ischaemic Attack	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
Altered State Of Consciousness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Basal Ganglia Haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Basilar Artery Thrombosis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Brain Compression	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Carotid Artery Aneurysm	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cerebellar Infarction	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Cerebellar Ischaemia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cerebral Haematoma	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Cerebral Ventricle Dilatation	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Embolic Stroke	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Encephalopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected382 at risk EG0010 events0 affected97 at risk
Epilepsy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected2 at risk
Facial Paresis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Haemorrhagic Stroke	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Hydrocephalus	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Peroneal Nerve Palsy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Slow Response To Stimuli	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Status Epilepticus	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Subarachnoid Haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00015 events14 affected382 at risk EG0016 events6 affected97 at risk
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected382 at risk EG0013 events3 affected97 at risk
Septic Shock	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected382 at risk EG0010 events0 affected97 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
CNS Ventriculitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Eye Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Implant Site Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Paronychia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Serratia Bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Staphylococcal Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Streptococcal Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Subdural Empyema	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Tracheostomy Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Urosepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00010 events10 affected382 at risk EG0012 events2 affected97 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 events7 affected382 at risk EG0011 events1 affected97 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 events7 affected382 at risk EG0011 events1 affected97 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 events3 affected382 at risk EG0010 events0 affected97 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Acute Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Bronchial Secretion Retention	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Respiratory Acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Respiratory Arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cardiac Failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0013 events3 affected97 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0012 events2 affected97 at risk
Myocardial Infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0012 events2 affected97 at risk
Cardiogenic Shock	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected382 at risk EG0010 events0 affected97 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Cardiac Arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Right Ventricular Failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0011 events1 affected97 at risk
Atrial Thrombosis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
Bradycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Atrial Flutter	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Atrioventricular Block	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Atrioventricular Block Complete	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cardiac Ventricular Thrombosis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Coronary Artery Disease	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Sinus Node Dysfunction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0006 events5 affected382 at risk EG0010 events0 affected97 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0011 events1 affected97 at risk
Arteriosclerosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Aorto-Duodenal Fistula	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Haematoma	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Haemorrhage	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Iliac Artery Occlusion	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Shock Haemorrhagic	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected382 at risk EG0012 events2 affected97 at risk
Melaena	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0011 events1 affected97 at risk
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Acute Abdomen	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Faecaloma	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Large Intestinal Haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Rectal Haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Multi-Organ Failure	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0012 events2 affected97 at risk
General Physical Health Deterioration	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Gait Disturbance	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Sudden Cardiac Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Sudden Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Swelling	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0006 events6 affected382 at risk EG0012 events2 affected97 at risk
Brain Herniation	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Cervical Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Lumbar Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Anaplastic Astrocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Bladder Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Brain Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Gastrointestinal Stromal Tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Lung Cancer Metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Pancreatic Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Prostate Cancer Metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
CSF Red Blood Cell Count Positive	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Electrocardiogram QT Prolonged	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Electroencephalogram Abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Liver Function Test Abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Transaminases Increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Troponin I Increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Heparin-Induced Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Haemorrhagic Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected382 at risk EG0010 events0 affected97 at risk
Renal Failure	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Urinary Retention	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Metabolic Syndrome	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Mental Status Changes	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected382 at risk EG0010 events0 affected97 at risk
Mental Disorder Due To A General Medical Condition	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Deafness	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Diplopia	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Ischaemic Hepatitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Social Stay Hospitalisation	Social circumstances	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected382 at risk EG0010 events0 affected97 at risk
Tracheostomy	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk
Ventricular Drainage	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected382 at risk EG0011 events1 affected97 at risk

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms