Trial NCT04409262
Publication Rosas, IO, Intensive Care Med, 2021 (published paper)
Dates: 2020-06-16 to 2021-01-04
Funding: Private (Hoffmann-La Roche)
Conflict of interest: Yes
Methods | |
RCT Blinding: double blinding | |
Location :
Multicenter / USA, Brazil, Russia, Spain Follow-up duration (days): 60 | |
Inclusion criteria | Patients with a positive SARS-CoV-2 polymerase chain reaction test result within 7 days of randomization; Pneumonia confirmed by chest x-ray or computed tomography; Hypoxemia requiring > 6 L/min supplemental oxygen; patients who received ≤ 2 doses of remdesivir before randomization. |
Exclusion criteria | Estimated glomerular filtration rate was < 30 mL/min (including patients undergoing hemodialysis or hemofiltration) or alanine aminotransferase or aspartate aminotransferase levels were > 5 × the upper limit of normal within 24 h of screening; Patients with suspected active bacterial, fungal, viral, or other infection except COVID-19. |
Interventions | |
Treatment
Placebo * |
|
Control
Tocilizumab ( / ) | |
Participants | |
Randomized 649 participants (n1=215 / n2= 434) | |
Characteristics of participants N=649 Mean age : 59.5 405 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=553 Critical: n=87 | |
Primary outcome | |
In the register Time from randomization to hospital discharge or "ready for discharge" up to Day 28 [ Time Frame: Up to Day 28 ] | |
In the report Time from randomization to hospital discharge or “ready for discharge,” defined as category 1, assessed by the investigator on the 7-category ordinal scale to day 28. | |
Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
General comment |
“In addition to the published article, the supplemental material, the study registry, protocol and statistical analysis plan were used in data extraction and risk of bias assessment. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518.) was also used. The authors have been contacted in order to obtain the results.
The primary outcome was modified after the start of the trial. "The primary outcome was initially defined as clinical status assessed by the investigator using a 7-category ordinal scale of clinical status on day 28, but this was changed to time from randomization to hospital discharge or “ready for discharge” to day 28 in response to evolving external data, including results from COVACTA and EMPACTA, which suggested that time to discharge was a more sensitive outcome for trials in this patient population." |