REMDACTA: A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT04409262
Collaborator
Gilead Sciences (Industry)
649
54
2
8.7
12
1.4
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
649 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia
Actual Study Start Date
:
Jun 16, 2020
Actual Primary Completion Date
:
Feb 1, 2021
Actual Study Completion Date
:
Mar 8, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Remdesivir + Tocilizumab (RDV+TCZ) Participants assigned to the RDV+TCZ arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ on Day 1. |
Drug: Remdesivir
Participants will receive intravenous (IV) RDV
Drug: Tocilizumab
Participants will receive IV TCZ
|
| Active Comparator: Remdesivir + Placebo (RDV+Placebo) Participants assigned to the RDV+ placebo arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ-placebo on Day 1. |
Drug: Remdesivir
Participants will receive intravenous (IV) RDV
Drug: Placebo
Participants will receive IV placebo matched to TCZ
|
Outcome Measures
Primary Outcome Measures
- Time to Hospital Discharge or "Ready for Discharge" up to Day 28 [Up to Day 28]
Defined as days from randomization to hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death. Hospital discharge or "Ready for Discharge" is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
Secondary Outcome Measures
- Time to Mechanical Ventilation or Death up to Day 28 [Up to Day 28]
Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event.
- Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 [Day 14]
Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Time to Death up to Day 28 [Up to Day 28]
Time to death is defined as the time from randomization to death.
- Time to Death up to Day 60 [Up to Day 60]
Time to death is defined as the time from randomization to death.
- Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28 [Up to Day 28]
Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28. Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 [Day 7]
Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 [Day 21]
Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 [Day 28]
Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 [Day 60]
Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) [Day 28 and Day 60]
Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event. Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event.
- Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) [Day 28 and Day 60]
- Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28 [Up to Day 28]
Participants who die by Day 28 are assigned a duration of 28 days.
- Difference in Mortality at Days 14, 28, and 60 [Days 14, 28, and 60]
- Time to Recovery up to Day 28 [Up to Day 28]
Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category >2 or death. Participants who die are censored at day 28. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28 [Up to Day 28]
Defined as hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death
- Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28 [Up to Day 28]
Participants already on mechanical ventilation at baseline are only counted as an event if death occurs.
Other Outcome Measures
- Percentage of Participants With Adverse Events (AEs) Tabulated by Severity [Up to Day 60]
AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE Participants are counted at the highest AE grade experienced.
- Proportion of Participants With Any Post-Treatment Infection [Up to Day 60]
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
-
Hospitalized with COVID-19 pneumonia confirmed per a positive polymerase chain reaction (PCR) of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
-
Requiring more than 6 L/min supplemental oxygen to maintain SpO2 > 93%
-
Agrees to not participate in another clinical trial for the treatment of COVID-19 while participating in this study
Exclusion Criteria
-
Known severe allergic reactions to tocilizumab or other monoclonal antibodies
-
Known hypersensitivity to remdesivir, the metabolites, or formulation excipients
-
Active tuberculosis (TB) infection
-
Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
-
In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
-
Treatment with immunosuppressive or immunomodulatory therapy (including tocilizumab) within the past 3 months
-
Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 within 24 hours prior to study drug dosing. In addition, participants with prior or current treatment with > 2 doses of remdesivir for COVID-19 are excluded
-
Participating in other drug clinical trials
-
Estimated glomerular filtration rate (eGFR) < 30 mL/min (including patients receiving hemodialysis or hemofiltration)
-
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN) detected within 24 hours of screening (according to local laboratory reference ranges)
-
Absolute neutrophil count (ANC) < 1000/uL at screening
-
Platelet count < 50,000/uL at screening
-
Body weight < 40 kg
-
Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Valleywise Health Medical Center | Phoenix | Arizona | United States | 85008 |
| 2 | eStudySite - Chula Vista - PPDS | Chula Vista | California | United States | 91911 |
| 3 | Hoag Hospital Irvine | Irvine | California | United States | 92612 |
| 4 | Providence St Johns Health Center | Santa Monica | California | United States | 90404 |
| 5 | Yale University School of Medicine; HIV Clinical Trials Program | New Haven | Connecticut | United States | 06501 |
| 6 | Medstar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 7 | Holy Cross Hospital Inc | Fort Lauderdale | Florida | United States | 33308 |
| 8 | Larkin Community Hospital Palm Springs Campus (Hialeah) | Hialeah | Florida | United States | 33012 |
| 9 | University of Miami Miller School of Medicine; Clinical Reseach Building | Miami | Florida | United States | 33136 |
| 10 | Larkin Community Hospital | South Miami | Florida | United States | 33143 |
| 11 | St Luke's Health System; Rheumatology Research | Boise | Idaho | United States | 83702 |
| 12 | Advocate Christ Medical Center | Oak Lawn | Illinois | United States | 60453 |
| 13 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
| 14 | University of Maryland | Baltimore | Maryland | United States | 21201 |
| 15 | Boston Medical Center | Boston | Massachusetts | United States | 02118-2393 |
| 16 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 17 | Henry Ford Medical Center | Novi | Michigan | United States | 48322 |
| 18 | St. Michael'S Medical Center | Newark | New Jersey | United States | 07102 |
| 19 | San Juan Oncology Associates | Farmington | New Mexico | United States | 87401 |
| 20 | Wyckoff Heights Medical Center | Staten Island | New York | United States | 11237 |
| 21 | Novant Health Clinical Research | Charlotte | North Carolina | United States | 28204 |
| 22 | OhioHealth Research Institute | Columbus | Ohio | United States | 43214 |
| 23 | Providence Saint Vincent's Medical Center | Portland | Oregon | United States | 97225 |
| 24 | Lehigh Valley Hospital | Allentown | Pennsylvania | United States | 18103 |
| 25 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 26 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 27 | The Liver Institute at Methodist Dallas | Arlington | Texas | United States | 76012 |
| 28 | Baylor Scott and White Medical Center - College Station | College Station | Texas | United States | 77845 |
| 29 | Baylor University Medical Center | Dallas | Texas | United States | 75231 |
| 30 | Baylor St. Luke's Medical Center | Houston | Texas | United States | 77030 |
| 31 | Ben Taub General Hospital - HCHD | Houston | Texas | United States | 77030 |
| 32 | Houston Methodist Hospital | Houston | Texas | United States | 77030 |
| 33 | Baylor Scott & White Medical Center - Irving | Irving | Texas | United States | 75061 |
| 34 | Baylor Scott & White Hospital - Plano | Plano | Texas | United States | 75093 |
| 35 | Baylor Scott & White Health | Temple | Texas | United States | 76502 |
| 36 | Intermountain LDS Hospital | Salt Lake City | Utah | United States | 84143 |
| 37 | The Providence Regional Medical Center Everett | Everett | Washington | United States | 98201 |
| 38 | West Virginia University Hospital | Morgantown | West Virginia | United States | 26506 |
| 39 | Santa Casa de Misericordia de Belo Horizonte | Belo Horizonte | MG | Brazil | 30150-221 |
| 40 | Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia | Curitiba | PR | Brazil | 80810-040 |
| 41 | Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ | Rio de Janeiro | RJ | Brazil | 21045-900 |
| 42 | CEMEC - Centro Multidisciplinar de Estudos Clínicos | Sao Bernardo Do Campo | SP | Brazil | 09715-090 |
| 43 | Hospital de Base de Sao Jose do Rio Preto | Sao Jose do Rio Preto | SP | Brazil | 15090-000 |
| 44 | Instituto de Infectologia Emilio Ribas | Sao Paulo | SP | Brazil | 01246-000 |
| 45 | Instituto do Coração - HCFMUSP | Sao Paulo | SP | Brazil | 05403-900 |
| 46 | Medsi Clinic | Moscow | Adygeja | Russian Federation | 143442 |
| 47 | O.M. Filatov City Clinical Hospital #15; Department of Surgery | Moskva | Moskovskaja Oblast | Russian Federation | 111539 |
| 48 | City Pokrovskaya Hospital | Sankt-peterburg | Sankt Petersburg | Russian Federation | 199106 |
| 49 | City Clinical Hospital # 52 | Moscow | Russian Federation | 123182 | |
| 50 | Hospital Universitario de Bellvitge | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 51 | Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas | Alcala de Henares | Madrid | Spain | 28005 |
| 52 | Hospital Universitario HM Torrelodones | Torrelodones | Madrid | Spain | 28250 |
| 53 | Hospital General Universitario de Guadalajara | Guadalajara | Spain | 19002 | |
| 54 | Hospital Universitario Fundacion Jimenez Diaz. | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Hoffmann-La Roche
- Gilead Sciences
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04409262
Other Study ID Numbers:
- WA42511
- 2020-002275-34
First Posted:
Jun 1, 2020
Last Update Posted:
Feb 14, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants with severe COVID-19 pneumonia |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) |
|---|---|---|
| Arm/Group Description | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of PBO on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of PBO was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of TCZ on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of TCZ was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. |
| Period Title: Overall Study | ||
| STARTED | 215 | 434 |
| COMPLETED | 140 | 300 |
| NOT COMPLETED | 75 | 134 |
Baseline Characteristics
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) | Total |
|---|---|---|---|
| Arm/Group Description | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of PBO on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of PBO was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of TCZ on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of TCZ was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | Total of all reporting groups |
| Overall Participants | 215 | 434 | 649 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
58.2
(13.6)
|
60.1
(13.3)
|
59.5
(13.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
73
34%
|
167
38.5%
|
240
37%
|
| Male |
142
66%
|
267
61.5%
|
409
63%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
125
58.1%
|
209
48.2%
|
334
51.5%
|
| Not Hispanic or Latino |
88
40.9%
|
208
47.9%
|
296
45.6%
|
| Unknown or Not Reported |
2
0.9%
|
17
3.9%
|
19
2.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
4
1.9%
|
4
0.9%
|
8
1.2%
|
| Asian |
5
2.3%
|
17
3.9%
|
22
3.4%
|
| Native Hawaiian or Other Pacific Islander |
3
1.4%
|
7
1.6%
|
10
1.5%
|
| Black or African American |
20
9.3%
|
52
12%
|
72
11.1%
|
| White |
154
71.6%
|
282
65%
|
436
67.2%
|
| More than one race |
2
0.9%
|
9
2.1%
|
11
1.7%
|
| Unknown or Not Reported |
27
12.6%
|
63
14.5%
|
90
13.9%
|
Outcome Measures
| Title | Time to Hospital Discharge or "Ready for Discharge" up to Day 28 |
|---|---|
| Description | Defined as days from randomization to hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death. Hospital discharge or "Ready for Discharge" is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+Placebo) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [days] |
14.0
|
14.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7414 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.965 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Mechanical Ventilation or Death up to Day 28 |
|---|---|
| Description | Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event. |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8993 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.980 | |
| Confidence Interval |
(2-Sided) 95% 0.72 to 1.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 |
|---|---|
| Description | Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 14 and were excluded from analysis for this endpoint. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 428 |
| Category 1 |
52.4
24.4%
|
54.0
12.4%
|
| Category 2 |
1.9
0.9%
|
2.6
0.6%
|
| Category 3 |
11.4
5.3%
|
8.9
2.1%
|
| Category 4 |
6.7
3.1%
|
9.6
2.2%
|
| Category 5 |
6.7
3.1%
|
4.9
1.1%
|
| Category 6 |
11.4
5.3%
|
10.0
2.3%
|
| Category 7 |
9.5
4.4%
|
10.0
2.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7648 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.05 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 1.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Death up to Day 28 |
|---|---|
| Description | Time to death is defined as the time from randomization to death. |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7867 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.948 | |
| Confidence Interval |
(2-Sided) 95% 0.65 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Death up to Day 60 |
|---|---|
| Description | Time to death is defined as the time from randomization to death. |
| Time Frame | Up to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+Placebo) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4602 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.882 | |
| Confidence Interval |
(2-Sided) 95% 0.63 to 1.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28 |
|---|---|
| Description | Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28. Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [Days] |
11.0
|
12.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8664 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.982 | |
| Confidence Interval |
(2-Sided) 95% 0.80 to 1.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 |
|---|---|
| Description | Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 7 and were excluded from analysis for this endpoint. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 428 |
| Category 1 |
21.9
10.2%
|
19.4
4.5%
|
| Category 2 |
4.3
2%
|
5.6
1.3%
|
| Category 3 |
17.6
8.2%
|
20.1
4.6%
|
| Category 4 |
30.0
14%
|
29.4
6.8%
|
| Category 5 |
9.5
4.4%
|
10.0
2.3%
|
| Category 6 |
12.9
6%
|
12.1
2.8%
|
| Category 7 |
3.8
1.8%
|
3.3
0.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9569 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 |
|---|---|
| Description | Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 21 and were excluded from analysis for this endpoint. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 428 |
| Category 1 |
62.4
29%
|
64.3
14.8%
|
| Category 2 |
1.4
0.7%
|
1.2
0.3%
|
| Category 3 |
4.8
2.2%
|
4.7
1.1%
|
| Category 4 |
2.9
1.3%
|
4.4
1%
|
| Category 5 |
6.7
3.1%
|
5.6
1.3%
|
| Category 6 |
7.1
3.3%
|
5.8
1.3%
|
| Category 7 |
14.8
6.9%
|
14.0
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6331 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.09 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 |
|---|---|
| Description | Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 28 and were excluded from analysis for this endpoint. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 428 |
| Category 1 |
67.1
31.2%
|
66.4
15.3%
|
| Category 2 |
1.4
0.7%
|
1.4
0.3%
|
| Category 3 |
1.0
0.5%
|
3.5
0.8%
|
| Category 4 |
2.9
1.3%
|
3.0
0.7%
|
| Category 5 |
4.3
2%
|
3.7
0.9%
|
| Category 6 |
3.8
1.8%
|
3.7
0.9%
|
| Category 7 |
19.5
9.1%
|
18.2
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9622 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.99 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 |
|---|---|
| Description | Clinical status was assessed by the investigator according to the following ordinal scale categories: Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 60 and were excluded from analysis for this endpoint. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 428 |
| Category 1 |
70.0
32.6%
|
72.2
16.6%
|
| Category 2 |
1.4
0.7%
|
0.7
0.2%
|
| Category 3 |
1.0
0.5%
|
1.4
0.3%
|
| Category 4 |
1.4
0.7%
|
1.6
0.4%
|
| Category 5 |
0.5
0.2%
|
0.7
0.2%
|
| Category 6 |
0
0%
|
0.7
0.2%
|
| Category 7 |
25.7
12%
|
22.7
5.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4850 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) |
|---|---|
| Description | Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event. Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event. |
| Time Frame | Day 28 and Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population for this endpoint included only participants not on mechanical ventilation at baseline |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 188 | 371 |
| Day 28 |
29.8
13.9%
|
27.5
6.3%
|
| Day 60 |
31.4
14.6%
|
28.8
6.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5915 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 95% -10.2 to 5.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 60 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5494 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -2.5 | |
| Confidence Interval |
(2-Sided) 95% -10.5 to 5.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) |
|---|---|
| Description | |
| Time Frame | Day 28 and Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population for this endpoint included only participants on mechanical ventilation at baseline. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 22 | 59 |
| Day 28 |
54.5
25.3%
|
40.7
9.4%
|
| Day 60 |
63.6
29.6%
|
47.5
10.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2590 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -14.1 | |
| Confidence Interval |
(2-Sided) 95% -37.4 to 9.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 60 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2290 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -14.6 | |
| Confidence Interval |
(2-Sided) 95% -37.0 to 7.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28 |
|---|---|
| Description | Participants who die by Day 28 are assigned a duration of 28 days. |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population for this endpoint included only participants on mechanical ventilation at baseline. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 22 | 59 |
| Mean (95% Confidence Interval) [Days] |
16.7
|
19.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2434 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.1125 | |
| Confidence Interval |
(2-Sided) 95% -2.16 to 8.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Difference in Mortality at Days 14, 28, and 60 |
|---|---|
| Description | |
| Time Frame | Days 14, 28, and 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Day 14 |
9.5
4.4%
|
10.0
2.3%
|
| Day 28 |
19.5
9.1%
|
18.1
4.2%
|
| Day 60 |
25.7
12%
|
22.6
5.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8222 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -4.4 to 5.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6944 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -7.8 to 5.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | Day 60 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3919 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -3.0 | |
| Confidence Interval |
(2-Sided) 95% -10.1 to 4.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Recovery up to Day 28 |
|---|---|
| Description | Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category >2 or death. Participants who die are censored at day 28. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Median (95% Confidence Interval) [Days] |
13.0
|
13.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6778 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.957 | |
| Confidence Interval |
(2-Sided) 95% 0.78 to 1.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28 |
|---|---|
| Description | Defined as hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen) Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen ICU, requiring intubation and mechanical ventilation ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) Death |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Number (95% Confidence Interval) [Percentage of participants] |
67.1
31.2%
|
66.0
15.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7692 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -8.7 to 6.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28 |
|---|---|
| Description | Participants already on mechanical ventilation at baseline are only counted as an event if death occurs. |
| Time Frame | Up to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - mITT Population | Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Arm/Group Description | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. | The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization. |
| Measure Participants | 210 | 430 |
| Number (95% Confidence Interval) [Percentage of participants] |
29.0
13.5%
|
28.6
6.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir + Placebo (RDV+Placebo) - mITT Population, Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9334 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted % difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -7.8 to 7.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity |
|---|---|
| Description | AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE Participants are counted at the highest AE grade experienced. |
| Time Frame | Up to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - Safety Population | Remdesivir + Tocilizumab (RDV+TCZ) - Safety Population |
|---|---|---|
| Arm/Group Description | The safety population included all participants who received any amount of study medication (RDV and/or TCZ/PBO), with participants grouped according to the actual treatment received rather than the treatment assigned at randomization. | The safety population included all participants who received any amount of study medication (RDV and/or TCZ/PBO), with participants grouped according to the actual treatment received rather than the treatment assigned at randomization. |
| Measure Participants | 213 | 429 |
| Grade 1 |
9.9
4.6%
|
10.5
2.4%
|
| Grade 2 |
21.1
9.8%
|
28.2
6.5%
|
| Grade 3 |
10.3
4.8%
|
11.2
2.6%
|
| Grade 4 |
4.2
2%
|
4.9
1.1%
|
| Grade 5 |
25.8
12%
|
22.6
5.2%
|
| Title | Proportion of Participants With Any Post-Treatment Infection |
|---|---|
| Description | |
| Time Frame | Up to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population. |
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) - Safety Population | Remdesivir + Tocilizumab (RDV+TCZ) - Safety Population |
|---|---|---|
| Arm/Group Description | The safety population included all participants who received any amount of study medication (RDV and/or TCZ/PBO), with participants grouped according to the actual treatment received rather than the treatment assigned at randomization. | The safety population included all participants who received any amount of study medication (RDV and/or TCZ/PBO), with participants grouped according to the actual treatment received rather than the treatment assigned at randomization. |
| Measure Participants | 213 | 429 |
| Serious infections |
27.7
12.9%
|
22.6
5.2%
|
| Infections |
35.7
16.6%
|
33.3
7.7%
|
| Opportunistic infections |
2.3
1.1%
|
1.4
0.3%
|
Adverse Events
| Time Frame | Up to Day 60 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population. | |||
| Arm/Group Title | Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) | ||
| Arm/Group Description | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of PBO on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of PBO was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of TCZ on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of TCZ was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | ||
All Cause Mortality |
||||
| Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 55/213 (25.8%) | 97/429 (22.6%) | ||
Serious Adverse Events |
||||
| Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 76/213 (35.7%) | 141/429 (32.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Bicytopenia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Blood loss anaemia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Heparin-induced thrombocytopenia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Normocytic anaemia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Thrombocytopenia | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Cardiac disorders | ||||
| Atrial fibrillation | 2/213 (0.9%) | 2 | 2/429 (0.5%) | 2 |
| Atrioventricular block complete | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Bradycardia | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Cardiac arrest | 3/213 (1.4%) | 3 | 2/429 (0.5%) | 2 |
| Cardiac failure | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Cardio-respiratory arrest | 2/213 (0.9%) | 2 | 1/429 (0.2%) | 1 |
| Cardiogenic shock | 0/213 (0%) | 0 | 3/429 (0.7%) | 3 |
| Chronic left ventricular failure | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Myocarditis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Pulseless electrical activity | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Right ventricular dysfunction | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Sinus bradycardia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Supraventricular tachycardia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Ventricular tachycardia | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal wall haematoma | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Colitis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Diverticular perforation | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Dysphagia | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Gastric ulcer perforation | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Gastrointestinal haemorrhage | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Intestinal ischaemia | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Pancreatitis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Pneumoperitoneum | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Rectal haemorrhage | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Retroperitoneal haemorrhage | 0/213 (0%) | 0 | 3/429 (0.7%) | 3 |
| Small intestinal obstruction | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| General disorders | ||||
| Brain death | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Catheter site haemorrhage | 1/213 (0.5%) | 1 | 2/429 (0.5%) | 3 |
| Death | 1/213 (0.5%) | 1 | 2/429 (0.5%) | 2 |
| Hypothermia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Multiple organ dysfunction syndrome | 2/213 (0.9%) | 2 | 2/429 (0.5%) | 2 |
| Hepatobiliary disorders | ||||
| Acute hepatic failure | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Cholecystitis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Hepatic failure | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Hepatitis acute | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Liver injury | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Infections and infestations | ||||
| Bacteraemia | 2/213 (0.9%) | 3 | 0/429 (0%) | 0 |
| Bacterial sepsis | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| COVID-19 | 8/213 (3.8%) | 8 | 14/429 (3.3%) | 14 |
| COVID-19 pneumonia | 27/213 (12.7%) | 27 | 36/429 (8.4%) | 36 |
| Clostridium difficile infection | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Device related sepsis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Enterobacter bacteraemia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Enterobacter infection | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Fungaemia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Pneumonia | 6/213 (2.8%) | 6 | 21/429 (4.9%) | 22 |
| Pneumonia acinetobacter | 1/213 (0.5%) | 1 | 2/429 (0.5%) | 2 |
| Pneumonia bacterial | 4/213 (1.9%) | 4 | 5/429 (1.2%) | 5 |
| Pneumonia klebsiella | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Pneumonia pseudomonal | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Pulmonary sepsis | 2/213 (0.9%) | 2 | 1/429 (0.2%) | 1 |
| Sepsis | 6/213 (2.8%) | 7 | 11/429 (2.6%) | 13 |
| Septic shock | 10/213 (4.7%) | 10 | 23/429 (5.4%) | 23 |
| Staphylococcal infection | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Systemic candida | 2/213 (0.9%) | 2 | 0/429 (0%) | 0 |
| Tracheobronchitis | 2/213 (0.9%) | 2 | 1/429 (0.2%) | 1 |
| Urinary tract infection | 3/213 (1.4%) | 3 | 4/429 (0.9%) | 4 |
| Urosepsis | 2/213 (0.9%) | 2 | 0/429 (0%) | 0 |
| Vascular device infection | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Brain herniation | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Investigations | ||||
| Aspartate aminotransferase increased | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Blood culture positive | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Hepatic enzyme increased | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Platelet count decreased | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Transaminases increased | 3/213 (1.4%) | 3 | 1/429 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Acidosis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Hypernatraemia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Hyponatraemia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Lactic acidosis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Metabolic acidosis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Nervous system disorders | ||||
| Aphasia | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Brain compression | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Brain oedema | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Cerebral haemorrhage | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Cerebrovascular accident | 2/213 (0.9%) | 2 | 5/429 (1.2%) | 5 |
| Embolic stroke | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Encephalopathy | 1/213 (0.5%) | 1 | 5/429 (1.2%) | 5 |
| Haemorrhage intracranial | 2/213 (0.9%) | 2 | 0/429 (0%) | 0 |
| Haemorrhagic stroke | 2/213 (0.9%) | 2 | 1/429 (0.2%) | 1 |
| Haemorrhagic transformation stroke | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Hypoxic-ischaemic encephalopathy | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Ischaemic stroke | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Neurotoxicity | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Presyncope | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Toxic encephalopathy | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Psychiatric disorders | ||||
| Mental status changes | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 14/213 (6.6%) | 14 | 21/429 (4.9%) | 21 |
| Renal failure | 0/213 (0%) | 0 | 5/429 (1.2%) | 5 |
| Renal impairment | 5/213 (2.3%) | 5 | 1/429 (0.2%) | 1 |
| Renal injury | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Atelectasis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Bronchospasm | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Dyspnoea | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Epistaxis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Hypoxia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Interstitial lung disease | 0/213 (0%) | 0 | 3/429 (0.7%) | 3 |
| Pneumomediastinum | 1/213 (0.5%) | 1 | 5/429 (1.2%) | 5 |
| Pneumonia aspiration | 0/213 (0%) | 0 | 3/429 (0.7%) | 3 |
| Pneumothorax | 1/213 (0.5%) | 1 | 7/429 (1.6%) | 7 |
| Pneumothorax spontaneous | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Pulmonary congestion | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Pulmonary embolism | 3/213 (1.4%) | 3 | 5/429 (1.2%) | 5 |
| Pulmonary fibrosis | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Respiratory acidosis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Respiratory failure | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 0/213 (0%) | 0 | 1/429 (0.2%) | 1 |
| Rash | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Subcutaneous emphysema | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
| Vascular disorders | ||||
| Aortic thrombosis | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Deep vein thrombosis | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Haematoma | 1/213 (0.5%) | 1 | 1/429 (0.2%) | 1 |
| Haemodynamic instability | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Hypertension | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Hypotension | 4/213 (1.9%) | 4 | 4/429 (0.9%) | 4 |
| Hypovolaemic shock | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Peripheral ischaemia | 1/213 (0.5%) | 1 | 0/429 (0%) | 0 |
| Shock | 0/213 (0%) | 0 | 4/429 (0.9%) | 4 |
| Shock haemorrhagic | 0/213 (0%) | 0 | 2/429 (0.5%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Remdesivir + Placebo (RDV+PBO) | Remdesivir + Tocilizumab (RDV+TCZ) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/213 (32.9%) | 144/429 (33.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 14/213 (6.6%) | 15 | 13/429 (3%) | 13 |
| Gastrointestinal disorders | ||||
| Constipation | 25/213 (11.7%) | 25 | 54/429 (12.6%) | 54 |
| Infections and infestations | ||||
| Urinary tract infection | 11/213 (5.2%) | 11 | 20/429 (4.7%) | 21 |
| Investigations | ||||
| Transaminases increased | 10/213 (4.7%) | 10 | 25/429 (5.8%) | 25 |
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 9/213 (4.2%) | 9 | 22/429 (5.1%) | 22 |
| Hypokalaemia | 6/213 (2.8%) | 9 | 23/429 (5.4%) | 26 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 11/213 (5.2%) | 11 | 24/429 (5.6%) | 25 |
| Vascular disorders | ||||
| Hypotension | 12/213 (5.6%) | 12 | 19/429 (4.4%) | 19 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann - La Roche |
| Phone | 1-800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04409262
Other Study ID Numbers:
- WA42511
- 2020-002275-34
First Posted:
Jun 1, 2020
Last Update Posted:
Feb 14, 2022
Last Verified:
Jan 1, 2022