Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting (NCT NCT04501952)

NCT ID: NCT04501952

Last Updated: 2021-11-16

Results Overview

The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

584 participants

Primary outcome timeframe

Randomization up to Day 28

Results posted on

2021-11-16

Participant Flow

Participants were enrolled at study sites in Europe and the United States. The first participant was screened on 18 September 2020. The last study visit occurred on 06 May 2021.

630 participants were screened.

Participant milestones

Participant milestones
Measure	Remdesivir (RDV) Participants received a single dose of intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo Participants received IV placebo to match (PTM) RDV on Days 1 to 3.
Overall Study STARTED	292	292
Overall Study COMPLETED	266	272
Overall Study NOT COMPLETED	26	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Remdesivir (RDV) Participants received a single dose of intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo Participants received IV placebo to match (PTM) RDV on Days 1 to 3.
Overall Study Adverse Event	0	3
Overall Study Investigator's Discretion	0	1
Overall Study Protocol Violation	1	1
Overall Study Withdrew Consent	5	4
Overall Study Lost to Follow-up	7	2
Overall Study Randomized and Never Treated	13	9

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.	Total n=562 Participants Total of all reporting groups
Age, Continuous	50 Years STANDARD_DEVIATION 15.3 • n=5 Participants	51 Years STANDARD_DEVIATION 14.8 • n=7 Participants	50 Years STANDARD_DEVIATION 15.1 • n=5 Participants
Sex: Female, Male Female	131 Participants n=5 Participants	138 Participants n=7 Participants	269 Participants n=5 Participants
Sex: Female, Male Male	148 Participants n=5 Participants	145 Participants n=7 Participants	293 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	15 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	228 Participants n=5 Participants	224 Participants n=7 Participants	452 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Permitted	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	123 Participants n=5 Participants	112 Participants n=7 Participants	235 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	146 Participants n=5 Participants	158 Participants n=7 Participants	304 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	264 Participants n=5 Participants	267 Participants n=7 Participants	531 Participants n=5 Participants
Region of Enrollment Denmark	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United Kingdom	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Spain	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization up to Day 28

Population: Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization (Defined as at Least 24 Hours of Acute Care) or All-Cause Death by Day 28	0.7 percentage of participants	5.4 percentage of participants

PRIMARY outcome

Timeframe: First dose date up to last dose date (maximum: 3 days) plus 30 days

Population: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.

TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.

Outcome measures

Outcome measures
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	42.3 percentage of participants	46.3 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 28

Population: Modified Full Analysis Set included all participants who were randomized into the study, and received at least 1 dose of study treatment, and enrolled under protocol amendment 2 or later.

The composite outcome of COVID-19 related MAVs or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Remdesivir n=246 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=252 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With COVID-19 Related Medical Visits Attended in Person by the Participant and a Health Care Professional (MAVs) or All-Cause Death by Day 28	1.7 percentage of participants	8.5 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 28

Population: Participants in the Full Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	Remdesivir n=266 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=274 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants Who Died by Day 28	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 28

Population: Participants in the Full Analysis Set were analyzed.

COVID-19 related hospitalization is defined as at least 24 hours of acute care derived by COVID-19 related hospitalization reported by the site. The percentage of the outcome and the corresponding 95% confidence interval were from Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With COVID-19 Related Hospitalization at Day 28	0.7 percentage of participants Interval 0.2 to 2.9	5.4 percentage of participants Interval 3.3 to 8.7

SECONDARY outcome

Timeframe: Randomization up to Day 14

Population: Participants in the Full Analysis Set were analyzed.

The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14	0.7 percentage of participants	5.4 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 14

Population: Participants in the modified Full Analysis Set were analyzed.

The composite outcome of COVID-19 related MAVs or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Remdesivir n=246 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=252 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14	0.8 percentage of participants	8.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: Participants in the Virology Analysis Set (all the participants who were randomized into the study, received at least 1 dose of study treatment, and had positive SARS-CoV-2 viral load at baseline) with available data were analyzed.

The time-weighted average change from baseline to study Day 7 (DAVG7) in SARS-CoV-2 viral load is defined as the time-weighted average between the first postbaseline value through the last available value up to Day 7 minus the baseline value in SARS-CoV-2 viral load (log10 copies/mL). DAVG7 is calculated using the trapezoidal rule and the area under the curve (AUC). For participants with data through days prior to Day 7, the time-weighted average change used data up to last available timepoint. If there was no postbaseline data, the participant was excluded from the analysis.

Outcome measures

Outcome measures
Measure	Remdesivir n=211 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=208 Participants Participants received IV PTM RDV on Days 1 to 3.
Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7	-1.24 log10 copies/ mililiter (mL) Standard Deviation 1.123	-1.14 log10 copies/ mililiter (mL) Standard Deviation 1.099

SECONDARY outcome

Timeframe: First Dose Date up to Day 14

Population: Participants in the Full Analysis Set with available data were analyzed.

The COVID-19-adapted FLU-PRO Plus is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild). Time to alleviation of baseline COVID-19 symptoms is defined (in days) as: First Date of the two consecutive dates achieving alleviation - First dose Date + 1. If a participant had not achieved symptom alleviation at last FLU-PRO Plus assessment or early discontinuation of study, the participant was censored at last FLU-PRO Plus assessment date.

Outcome measures

Outcome measures
Measure	Remdesivir n=66 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=60 Participants Participants received IV PTM RDV on Days 1 to 3.
Time to Alleviation (Mild or Absent) of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted Influenza Patient-Reported Outcome Plus Questionnaire (FLU-PRO Plus)	NA days Interval 10.0 to Not enough event to estimate Median and Inter-Quartile Range	NA days Interval 13.0 to Not enough event to estimate Median and Inter-Quartile Range

SECONDARY outcome

Timeframe: First dose date up to Day 28

Population: Participants in the Full Analysis Set with available data were analyzed.

The worsening after alleviation of baseline COVID-19 symptoms is defined as for a participant who has achieved alleviation of baseline COVID-19 symptoms, if symptom scored as 2 or higher at baseline is scored as 2 or higher postbaseline after achieved alleviation, or symptoms scored as 1 at baseline are scored as 1 or higher postbaseline after achieved alleviation. The COVID-19-adapted FLU-PRO Plus was used. It is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild).

Outcome measures

Outcome measures
Measure	Remdesivir n=23 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=15 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire	30.4 percentage of participants	13.3 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to Day 28

Population: Participants in the Full Analysis Set were analyzed.

Outcome measures

Outcome measures
Measure	Remdesivir n=279 Participants Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 Participants Participants received IV PTM RDV on Days 1 to 3.
Percentage of Participants Who Required Oxygen Supplementation by Day 28	0.4 percentage of participants	1.8 percentage of participants

Adverse Events

Remdesivir

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Placebo

Serious events: 19 serious events

Other events: 49 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Remdesivir n=279 participants at risk Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 participants at risk Participants received IV PTM RDV on Days 1 to 3.
Gastrointestinal disorders Nausea	10.8% 30/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	7.4% 21/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Nervous system disorders Headache	5.7% 16/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	6.0% 17/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Cough	3.6% 10/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	6.4% 18/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Remdesivir n=279 participants at risk Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Placebo n=283 participants at risk Participants received IV PTM RDV on Days 1 to 3.
Cardiac disorders Acute myocardial infarction	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Cardiac disorders Angina pectoris	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Cardiac disorders Atrial fibrillation	0.72% 2/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.00% 0/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Cardiac disorders Cardiac failure congestive	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.00% 0/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Cardiac disorders Mitral valve prolapse	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Infections and infestations Covid-19	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.71% 2/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Infections and infestations Covid-19 pneumonia	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	2.5% 7/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Infections and infestations Pneumonia	0.72% 2/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	1.1% 3/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Infections and infestations Viral myocarditis	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.00% 0/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Investigations Fibrin D dimer increased	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	1.1% 3/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.35% 1/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
Vascular disorders Blood pressure inadequately controlled	0.36% 1/279 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.	0.00% 0/283 • Adverse Events: First dose date up to 3 days plus 30 days; All-Cause Mortality: Randomization to the end of study (maximum: 59 days) Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment; All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.