Trial NCT04372186
Publication Salama C, N Engl J Med, 2020 (published paper)
Dates: 2020-05-14 to 2020-08-18
Funding: Private (Genentech, Inc.)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / Brazil, Kenya, Mexico, Peru, South Africa, USA Follow-up duration (days): 60 | |
| Inclusion criteria | 1) Patients ≥18 years of age (with no upper age limit)
2) Hospitalized with Covid-19 pneumonia confirmed by a positive polymerase chain reaction test and radiographic imaging 3) Blood oxygen saturation <94% on ambient air |
| Exclusion criteria | 1) If they required continuous positive airway pressure, bilevel positive airway pressure, or mechanical ventilation.
2) If progression to death was imminent and inevitable within 24 hours as determined by the treating physician 3) Active tuberculosis or suspected active bacterial, fungal, or viral infection (other than SARS-CoV-2 or well-controlled HIV). 4) Patients with comorbidities were not excluded unless the investigator determined it would preclude safe patient participation. |
| Interventions | |
| Treatment
Tocilizumab 8 mg/kg IV, maximum 800 mg, a second infusion could be administered 8 to 24 hours after the first one. |
|
| Control
Placebo Duration : 1 day | |
| Participants | |
| Randomized 388 participants (n1=259 / n2= 129) | |
| Characteristics of participants N=388 Mean age : 55.9 223 males Severity : Mild: n=35 / Moderate: n=242/ Severe: n=100 Critical: n=0 | |
| Primary outcome | |
| In the register Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28 [ Time Frame: Up to Day 28 ] | |
| In the report Mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by 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 pre-print article, study registry, protocol, statistical analysis plan and supplementary appendix were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry and protocol version 1 primary outcome (cumulative proportion of mechanical ventilation) does not reflect the primary outcome reported in the paper and and protocol version 2 (cumulative proportion of mechanical ventilation or death). Some secondary outcomes reported in the registry were not reported in the manuscript.
On December 21st,2020, we received additional information from authors on this study, we updated the study results based on authors reply. The study was updated on January 13th, 2021 with data from the New England Journal of Medicine publication. The definition for clinical improvement was 'at least a two-category improvement in clinical status relative to baseline on the seven-category ordinal scale (for patients in category 2 at baseline, those with a clinical status of category 1 were considered to have met the threshold)' and the data now corresponds to this definition. |