Trial NCT04315948, EudraCT2020-000936-23
Publication Ader F, medRxiv, 2022 (published paper)
Dates: 2020-03-22 to 2021-01-21
Funding: Public/non profit (European Union Commission, French Ministry of Health, DIM One Health Île-de France, REACTing, Fonds Erasme-COVID-ULB, Belgian Health Care Knowledge Centre (KCE))
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Austria, Belgium, France, Luxembourg, Portugal Follow-up duration (days): 90 | |
| Inclusion criteria | Hospitalised participants ≥18 years of age; laboratory-confirmed SARS-CoV-2 infection; illness of any duration; at least one of the following: clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air, or requirement of supplemental oxygen, high flow oxygen devices, non-invasive ventilation and/or mechanical ventilation; women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study; written informed consent |
| Exclusion criteria | Liver enzymes (ALT/AST) > 5 times the upper limit of normal; stage 4 severe chronic kidney disease or requiring dialysis (eGFR < 30 mL/min); anticipated transfer to another hospital which is not a study site within 72 hours; contraindication to any study medication including allergy; treated with one of the evaluated antivirals in the in the past 29 days or used ribavirin in the 29 days and/or concomitantly to randomisation; pregnant or breast-feeding women |
| Interventions | |
| Treatment
Remdesivir Initial dose: 200 mg IV on the first day -Maintenance dose: 100 mg IV once a day for 5-9 days |
|
| Control
Standard care Definition of Standard care: Corticosteroids and anticoagulants were added to the standard of care on Oct1,2020 (protocolversion10.0). The suggested corticosteroids regimen was dexamethasone 6 mg once daily for 10 days or until discharge. In participants who were critically ill with acute respiratory distress syndrome requiring intensive care unit admission, a standard acute respiratory distress syndrome dexa- methasone regimen could be proposed at the clinician’s discretion (dexamethasone 20 mg once daily for 5 days, followed by 10 mg once daily for 5 days).Dosage regimens of anticoagulation were administered according to local protocols for venous thromboembolism prophylaxis or therapy. Other supportive treatments, such as immunomodulatory agents, were allowed in all groups and left to the investigator’s discretion. No participant received a SARS-CoV-2 vaccine during the course of the trial. | |
| Participants | |
| Randomized 857 participants (n1=429 / n2= 428) | |
| Characteristics of participants N=857 Mean age : NR 588 males Severity : Mild: n=15 / Moderate: n=482/ Severe: n=192 Critical: n=154 | |
| Primary outcome | |
| In the register Percentage of subjects reporting each severity rating on a 7-point ordinal scale [ Time Frame: Day 15 ] | |
| In the report Clinical status at day 15 as measured on the 7-point ordinal scale of the WHO | |
| 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 pre-print/published article, the published protocol, supplementary appendices, prospective online trial registries and data gained from contact with authors were used in data analysis and risk of bias assessment. The pre-print reported on an interim analysis for the remdesivir intervention arm of a multiple-arm platform study (DisCoVeRy, an add-on trial to the WHO Solidarity consortium) that was terminated early due to futility. Consequently, the planned sample size was not achieved and long-term outcomes were not reported. Other than that, there were no substantial changes to procedures, population, or interventions. The outcome WHO Score 7 or above includes participants with events within 28 days rather than at 28 days. Mortality at day 28 was reported but not extracted due to overlapping patient population with Pan, N Engl J Med, 2020.
On 12th of July, 2021, this study was updated based on updated pre-print. On 6th of October, 2021, this study was updated based on the published article. On 16th of November, 2021, this study was updated based on data from contact with authors. On 14th of April, 2022, this study was updated based on the preprint reporting on the final results. |