Trial NCT04315948, EudraCT2020-000936-23
Publication Ader F, Lancet Infect Dis, 2021 (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
Multicenter / Austria, Belgium, France, Luxembourg, Portugal |
Follow-up duration (days): 28
|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|
Initial dose: 200 mg IV on the first day -Maintenance dose: 100 mg IV once a day for 5-9 days
Definition of Standard care: Corticosteroids and anticoagulants were added to the standardofcareonOct1,2020(protocolversion10.0).The suggested corticosteroids regimen was dexamethasone 6 mg once daily for 10 days or until discharge.11,12 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).13 Dosage regimens of anticoagulation were administered according to local protocols for venous thromboembolism prophy- laxis or therapy.14,15 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.
857 participants (n1=429 / n2= 428)
|Characteristics of participants|
Mean age : NR
Severity : Mild: n=16 / Moderate: n=485/ Severe: n=183 Critical: n=148
|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
Yes. In English
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
In addition to the pre-print/published article, the published protocol, supplementary appendices and prospective online trial registries 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.
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.