This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
452
Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen or show no improvement.
Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 28 (Week 4)
Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or "ready for discharge") 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 7. \- Death
Time frame: Day 28
Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours
Defined as time from first dose of study drug to at least two NEWS2 assessments with a score of \<=2 covering a span of at least 21.5 hours, with a maximum of 26.5 hours between the first and last of these assessments and no assessments with a score \>2 in between. If one of the components of the NEWS2 score was missing at a particular time point, then the NEWS2 score was not calculated. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
Time to improvement for this outcome measure was defined as the days from the first dose of study drug to when at least a 2-category improvement in clinical status (based on a 7-category ordinal scale) is observed. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Time to Hospital Discharge or "Ready for Discharge"
Time to Hospital Discharge was defined as the time from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</=2L supplemental oxygen) Participants who died were censored at Day 28.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of California San Diego
La Jolla, California, United States
eStudySite
La Mesa, California, United States
David Geffen School of Medicine UCLA
Los Angeles, California, United States
Stanford University
Stanford, California, United States
Denver Health Medical Center
Denver, Colorado, United States
University of Miami Miller School of Medicine
Miami, Florida, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Ochsner Clinic Foundation
Baton Rouge, Louisiana, United States
Baystate Health System
Springfield, Massachusetts, United States
...and 52 more locations
Time frame: Up to Day 28
Incidence of Mechanical Ventilation by Day 28
Participants who died by Day 28 were assumed to have required mechanical ventilation.
Time frame: Up to Day 28
Ventilator-Free Days to Day 28
Participants who died by Day 28 were assigned 0 ventilator-free days.
Time frame: Up to Day 28
Incidence of Intensive Care Unit (ICU) Stay by Day 28 (Week 4)
Participants who died by Day 28 were assumed to have required an ICU stay.
Time frame: Up to Day 28
Duration of ICU Stay to Day 28 (Week 4)
Participants who died by Day 28 were assigned a duration from the first dose of study drug to Day 28 at hour 23:59:59.
Time frame: Up to Day 28
Clinical Status Assessed Using a 7-Category Ordinal Scale at Day 14
Clinical status was assessed using a 7-category ordinal scale: 1. \- Discharged (or "ready for discharge") 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 7. \- Death
Time frame: Day 14
Time to Clinical Failure to Day 28 (Week 4)
Time to clinical failure was defined as the number of days from the first dose of study drug to the first occurrence on study of death, mechanical ventilation, ICU admission, or study withdrawal prior to discharge, whichever occurs first.
Time frame: Up to Day 28
Mortality Rate at Day 28 (Week 4)
Time frame: Day 28
Time to Recovery to Day 28 (Week 4)
Time to recovery was defined as the number of days from the first dose of study drug to hospital discharge or "ready for discharge" (normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) or non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen. Participants who died were censored at Day 28.
Time frame: Up to Day 28
Duration of Supplemental Oxygen to Day 28 (Week 4)
Participants who died by Day 28 were assigned a duration of 28 days of supplemental oxygen.
Time frame: Up to Day 28