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
- Conditions
- COVID-19 Pneumonia
- Interventions
- Registration Number
- NCT04409262
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 649
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remdesivir + Tocilizumab (RDV+TCZ) Remdesivir Participants assigned to the RDV+TCZ arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ on Day 1. Remdesivir + Placebo (RDV+Placebo) 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. Remdesivir + Tocilizumab (RDV+TCZ) Tocilizumab Participants assigned to the RDV+TCZ arm will receive a 10-day treatment course of RDV, plus one infusion of TCZ on Day 1. Remdesivir + Placebo (RDV+Placebo) Remdesivir 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.
- Primary Outcome Measures
Name Time Method 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.
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. Death
- Secondary Outcome Measures
Name Time Method 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.
Time to Death up to Day 60 Up to Day 60 Time to death is defined as the time from randomization to 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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathClinical 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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathProportion 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 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.
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathProportion 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.
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathProportion 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.
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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathTime to Death up to Day 28 Up to Day 28 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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathClinical 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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathClinical 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:
1. Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen)
2. Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
3. Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
5. ICU, requiring intubation and mechanical ventilation
6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
7. DeathProportion 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.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.
Trial Locations
- Locations (54)
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Baylor Scott & White Medical Center - Irving
🇺🇸Irving, Texas, United States
Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia
🇧🇷Curitiba, PR, Brazil
Hospital de Base de Sao Jose do Rio Preto
🇧🇷Sao Jose do Rio Preto, SP, Brazil
O.M. Filatov City Clinical Hospital #15; Department of Surgery
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Novant Health Clinical Research
🇺🇸Charlotte, North Carolina, United States
The Providence Regional Medical Center Everett
🇺🇸Everett, Washington, United States
Baylor Scott & White Hospital - Plano
🇺🇸Plano, Texas, United States
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷Sao Bernardo Do Campo, SP, Brazil
Baylor Scott and White Medical Center - College Station
🇺🇸College Station, Texas, United States
City Pokrovskaya Hospital
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Instituto de Pesquisa Clinica Evandro Chagas - IPEC FIOCRUZ
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital Universitario Principe de Asturias; Medicina Interna - Servicio de Enfermedades Infecciosas
🇪🇸Alcala de Henares, Madrid, Spain
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, MG, Brazil
City Clinical Hospital # 52
🇷🇺Moscow, Russian Federation
Hospital Universitario HM Torrelodones
🇪🇸Torrelodones, Madrid, Spain
Hospital General Universitario de Guadalajara
🇪🇸Guadalajara, Spain
University of Maryland
🇺🇸Baltimore, Maryland, United States
Hoag Hospital Irvine
🇺🇸Irvine, California, United States
Holy Cross Hospital Inc
🇺🇸Fort Lauderdale, Florida, United States
Providence St Johns Health Center
🇺🇸Santa Monica, California, United States
Larkin Community Hospital Palm Springs Campus (Hialeah)
🇺🇸Hialeah, Florida, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Henry Ford Medical Center
🇺🇸Novi, Michigan, United States
St. Michael'S Medical Center
🇺🇸Newark, New Jersey, United States
Wyckoff Heights Medical Center
🇺🇸Staten Island, New York, United States
OhioHealth Research Institute
🇺🇸Columbus, Ohio, United States
The Liver Institute at Methodist Dallas
🇺🇸Arlington, Texas, United States
Ben Taub General Hospital - HCHD
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Intermountain LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Baylor Scott & White Health
🇺🇸Temple, Texas, United States
eStudySite - Chula Vista - PPDS
🇺🇸Chula Vista, California, United States
St Luke's Health System; Rheumatology Research
🇺🇸Boise, Idaho, United States
University of Miami Miller School of Medicine; Clinical Reseach Building
🇺🇸Miami, Florida, United States
Larkin Community Hospital
🇺🇸South Miami, Florida, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
Instituto de Infectologia Emilio Ribas
🇧🇷Sao Paulo, SP, Brazil
Instituto do Coração - HCFMUSP
🇧🇷Sao Paulo, SP, Brazil
Medsi Clinic
🇷🇺Moscow, Adygeja, Russian Federation
Hospital Universitario Fundacion Jimenez Diaz.
🇪🇸Madrid, Spain
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Medstar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Yale University School of Medicine; HIV Clinical Trials Program
🇺🇸New Haven, Connecticut, United States
Valleywise Health Medical Center
🇺🇸Phoenix, Arizona, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Providence Saint Vincent's Medical Center
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States