Plitidepsin Versus Control in Immunocompromised Adult Par... | NCT05705167

ID	Type	Description	Link
2022-002489-34	EudraCT Number

Label	Type	Description	Intervention Names
Plitidepsin 2.5 mg	Experimental	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute intravenous (IV) infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) will be administered to participants of the following groups: Group 1 - Participants receiving immune-suppression due to haematopoietic or organ transplantation. Group 2 - Participants receiving B-cell depleting therapies. Group 3 - Participants receiving other immune-suppressive therapies. Group 4 - Other situations with immune deficiencies.	Drug: Plitidepsin
Control	No Intervention	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) will be administered to participants of the following groups: Group 1 - Participants receiving immune-suppression due to haematopoietic or organ transplantation. Group 2 - Participants receiving B-cell depleting therapies. Group 3 - Participants receiving other immune-suppressive therapies.

Name	Type	Description	Arm Group Labels	Other Names
Plitidepsin	Drug	IV infusion over 60-minutes	Plitidepsin 2.5 mg

Measure	Description	Time Frame
One-month All-cause Mortality Rate	In the event of the participant initiating another non-protocol therapy, 1-month all-cause mortality rate was evaluated regardless of initiation of new non-protocol therapy.	Day 1 to Day 30 (±2)

Measure	Description	Time Frame
Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30	Time to confirmed negativisation in SARS-CoV antigen test or RT-PCR Ct>30 was calculated as time from randomisation to the corresponding event using Kaplan-Meier (KM) estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
Participant aged ≥18 years.
Participant diagnosed COVID-19, with the following characteristics:
1. A regulatory-approved test, collected no more than 3 days prior to study randomisation, with either a Ct value ≤30 or a positive antigen test.
2. Presence of any of the selected signs/symptom listed in the COVID-19 signs/symptoms checklist within the last 24 hours.
Participant already admitted or requiring hospital care for symptomatic COVID-19, for which at least one antiviral has failed or cannot be used (i.e., contraindication, absence of labelled indication, guidelines or drug unavailability), after a minimum washout period of 24 hours for small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir, ritonavir) and 5 days for antiviral monoclonal antibodies (e.g., tixagevimab + cilgavimab) or convalescent plasma.
Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:
1. Absolute neutrophil count ≥500/mm^3 (0.5 x 109/L).
2. Platelet count ≥ 50 000/mm3 (50 x 109/L).
3. Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease).
4. Serum bilirubin ≤1.5 x ULN (or direct bilirubin <1.5 x ULN when total bilirubin is above ULN).
5. Estimated glomerular filtration rate ≥30 mL/min (CKD-EPI Creatinine Equation [2021]).
Females of child-bearing potential must have a negative serum or urine pregnancy test by local laboratory at screening and must be non-lactating.
Females of child-bearing potential and fertile males with partners of child-bearing potential must use contraceptive methods as specified in the protocol.

Group-specific inclusion criteria:

Group 1 - Patients receiving, within the last 30 days, immune-suppressive therapy due to haematopoietic or organ transplantation.
Group 2 - Participants receiving B-cell depleting therapies within the last 6 months (with the exception of CAR-T cell therapy for which time restriction is not applicable).
Group 3 - Participants receiving, within the last 30 days, other immune-suppressive therapies.
Group 4 - Other situations with immunodeficiency.
1. Primary immune deficiencies.
2. Human immunodeficiency virus (HIV) infection, with CD4^+ T lymphocyte < 200 cells/μL in the last month.
3. Radiation therapy within the last 3 months- requires documentation of ALC < 500 cells/μL.
4. Haematological neoplasia or myelodysplasia not currently receiving any therapy.
5. Other situations with a documentation of ALC < 500 cells/μL.

Exclusion Criteria:

Evidence of critical illness.
Any of the following cardiac conditions or risk factors:
1. Cardiac infarction or cardiac surgery episode within the last month.
2. History of known congenital QT prolongation.
3. Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (<50%).
4. Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).
Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or contraindication to receive dexamethasone, antihistamine H1/H2, or anti-serotoninergic 5HT3 agents.
Females who are pregnant or breast-feeding.
Females and males with partners of child-bearing potential who are not using at least 1 protocol-specified method of contraception.
Any situation currently requiring increasing needs of immune-suppressive agents.
Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the participant or potentially impact on participant compliance or the safety/efficacy observations in the study.
Participation in another clinical study involving an investigational drug within 30 days prior to screening.

Facility	Status	City	State	ZIP	Country	Contacts
Universitair Ziekenhuis Leuven - Campus Gasthuisberg		Leuven	Flemish Brabant	3000	Belgium
Cancer Research Centre of Lyon

PubMed Identifier	Type	Citation	Retractions
39182994	Derived	Landete P, Caliman-Sturdza OA, Lopez-Martin JA, Preotescu L, Luca MC, Kotanidou A, Villares P, Iglesias SP, Guisado-Vasco P, Saiz-Lou EM, Del Carmen Farinas-Alvarez M, de Lucas EM, Perez-Alba E, Cisneros JM, Estrada V, Hidalgo-Tenorio C, Poulakou G, Torralba M, Fortun J, Garcia-Ocana P, Lemaignen A, Marcos-Martin M, Molina M, Paredes R, Perez-Rodriguez MT, Raev D, Ryan P, Meira F, Gomez J, Torres N, Lopez-Mendoza D, Jimeno J, Varona JF. A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19. Clin Infect Dis. 2024 Oct 15;79(4):910-919. doi: 10.1093/cid/ciae227.

ID	Title	Description
FG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute intravenous (IV) infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 22, 2023	Oct 15, 2024

Arm/Group Information

ID	Title	Description
BG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
BG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
BG002	Group 2: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.
BG003	Group 2: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.
BG004	Group 3: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.
BG005	Group 3: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.
BG006	Group 4: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 4. Group 4 - Other situations with immune deficiencies.
BG007	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

One-month All-cause Mortality Rate

In the event of the participant initiating another non-protocol therapy, 1-month all-cause mortality rate was evaluated regardless of initiation of new non-protocol therapy.

FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.

Posted

Number

95% Confidence Interval

percentage of participants

Day 1 to Day 30 (±2)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG002	Group 2: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.
OG003	Group 2: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.
OG004	Group 3: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.
OG005	Group 3: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.
OG006	Group 4: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 4. Group 4 - Other situations with immune deficiencies.

Units	Counts
Participants	OG0002 OG0011 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.0(0.0 to 84.2) OG0010.0(0.0 to 97.5) OG00220.0(2.5 to 55.6) OG003

Secondary

Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30

Time to confirmed negativisation in SARS-CoV antigen test or RT-PCR Ct>30 was calculated as time from randomisation to the corresponding event using Kaplan-Meier (KM) estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.

Posted

Median

95% Confidence Interval

days

Day 1 to Day 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Secondary

Time to Sustained End of COVID-related Hospital Care

Time to sustained end of COVID-related hospital care from the time of randomisation was calculated as time from randomisation to the corresponding event using KM estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.

Posted

Median

95% Confidence Interval

days

Day 1 to Day 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Secondary

Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms

Time to sustained improvement and resolution of all targeted COVID-19 signs/symptoms was calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as the event occurring on the first of 4 consecutive days when all symptoms scored as National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0; category of moderate-severe intensity, or requiring medical intervention, or limiting instrumental activity of daily living are scored as mild or absent AND all symptoms scored mild or 0 (absent) at study entry are scored as 0. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.

Posted

Median

95% Confidence Interval

days

Day 1 to Day 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Secondary

Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS)

Distribution of participants according to their clinical status by the 11-category WHO CPS:

Uninfected; no viral ribonucleic acid (RNA) detected
Asymptomatic; viral RNA detected
Symptomatic; independent
Symptomatic; assistance needed
Hospitalised; no oxygen therapy
Hospitalised; oxygen by mask or nasal prongs
Hospitalised; oxygen by non-invasive ventilation (NIV) or high flow
Intubation and mechanical ventilation
Mechanical ventilation or vasopressors
Mechanical ventilation and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) OR
Death.

Posted

Count of Participants

Participants

Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Secondary

Number of Participants Requiring Oxygen Therapy

The maximum number of participants requiring oxygen therapy on any day during each visit window is reported.

Posted

Count of Participants

Participants

Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG002

Secondary

Time to Sustained Discontinuation of Oxygen Supplementation

Time to sustained discontinuation is calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as discontinuation of oxygen supplementation for at least 7 days. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.

Posted

Median

95% Confidence Interval

days

Day 1 to Day 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

Secondary

Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

Frequency of the following events (all-cause and treatment-related) are included:

TEAEs
TEAEs ≥ grade 3 according to the NCI CTCAE v5.0
TEAEs of special interest
Serious TEAEs
Serious adverse reactions (SARs)
AEs leading to treatment discontinuation
Deaths (related to COVID-19/all)

Clinically relevant/significant changes from Baseline in laboratory parameters and vital signs were reported as AEs.

As Treated Population: All participants who received any exposure to study treatment (plitidepsin or control). As Treated population was analysed according to the treatment they actually received.

Posted

Count of Participants

Participants

Day 1 to Day 60 (±3)

ID	Title	Description
OG000	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.
OG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.

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	Group 1: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.	0	2	1	2	1	2
EG001	Group 1: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1. Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation.	0	1	0	1	1	1
EG002	Group 2: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.	3	11	5	11	10	11
EG003	Group 2: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 2. Group 2 - Participants who received B-cell depleting therapies.	0	4	4	4	4	4
EG004	Group 3: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.	1	1	1	1	1	1
EG005	Group 3: Control	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 3. Group 3 - Participants who received other immune-suppressive therapies.	1	1	1	1	1	1
EG006	Group 4: Plitidepsin 2.5 mg	Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 4. Group 4 - Other situations with immune deficiencies.	1	8	2	8	6	8

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG0030 events0 affected4 at risk EG0040 events0 affected1 at risk EG0050 events0 affected1 at risk EG0060 events0 affected8 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Pneumoperitoneum	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Generalised oedema	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Bacterial sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Candida pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Device related infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Stenotrophomonas infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Tuberculosis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Coma	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0023 events2 affected11 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Embolism	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG0030 events0 affected4 at risk EG0040 events0 affected1 at risk EG0050 events0 affected1 at risk EG0062 events1 affected8 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Sinus arrhythmia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0025 events2 affected11 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0023 events3 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected1 at risk EG0020 events0 affected11 at risk EG003
Chills	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected1 at risk EG0022 events2 affected11 at risk EG003
Malaise	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Pain	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0027 events5 affected11 at risk EG003
Haemophagocytic lymphohistiocytosis	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Campylobacter infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Cystitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Respiratory syncytial virus infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Staphylococcal bacteraemia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Urinary tract infection enterococcal	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Procedural nausea	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected1 at risk EG0020 events0 affected11 at risk EG003
Blood creatinine increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Blood urea increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Cardiac murmur	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Urine output decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Weight decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
White blood cell count increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Lethargy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Migraine	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Slow speech	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Somnolence	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Agitation	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0023 events3 affected11 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Haematoma	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003
Hypotension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0022 events2 affected11 at risk EG003
Phlebitis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0021 events1 affected11 at risk EG003
Vein disorder	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected2 at risk EG0010 events0 affected1 at risk EG0020 events0 affected11 at risk EG003

ID	Term
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases