Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
Main result
- 397 patients were randomized (200 in the 5-day group [median treatment time of 5 days] and 197 in the 10-day group [median treatment time of 9 days]).
- At baseline, patients randomized to the 10-day group had significantly worse clinical status than those randomized to the 5-day group (P = 0.02).
- Endpoint: 64% of patients in the 5-day group and 54% of patients in the 10-day group improved clinical status at D14 by 2 or more points on the ordinal scale. However, clinical status at D14 was similar between the two groups after adjustment to baseline clinical status (p=0.14).
- The most common adverse events were nausea (9% of patients), worsening of respiratory failure (8%), increased ALT (7%) and constipation (7%).
- Discontinuation of treatment due to adverse events: 4% of the 5-day group and 11% of the 10-day group.
- At D14, 16 patients (8%) in the 5-day group and 21 patients (11%) in the 10-day group had died, and 120 (60%) and 103 (52%) were discharged from hospital, respectively.
Takeaways
Strength of evidence Weak
- Randomized, open-label Phase 3 therapeutic trial
- Full treatment not mandatory if clinical improvement allowing discharge
- Amendment of the protocol on 15 March with, in particular, modification of the main judging criterion and inclusion criteria.
- Trial designed and conducted by the sponsor (Gilead Sciences - the pharmaceutical company marketing remdesivir), who also collected the data, monitored the conduct of the trial and performed the statistical analyses. The first manuscript was written by an author employed by Gilead Sciences, with contributions from all authors.
- Complete treatment for 172/200 (86%) patients in the 5-day group and 86/197 (43.7%) in the 10-day group.
- No control group without redesigning
Objectives
Method
Phase 3 randomized, open-label therapeutic trial. Multicentric (55 hospitals) and international (USA, Italy, Spain, Germany, Hong Kong, Singapore, South Korea and Taiwan) study. Inclusion between March 6 and March 26.
Inclusion criteria:
- Patients aged at least 12 years, inpatient
- With a confirmed SARS-CoV-2 infection within 4 days prior to randomization
- Oxygen saturation ≤ 94% in ambient air or oxygen therapy
- And radiological signs of pneumonia.
Exclusion criteria: patient receiving mechanical ventilation, ECMO, with evidence of multiviscular failure, biological criteria (ALT or AST > 5N, estimated Cockcroft-Gault creatinine clearance<50 mL/min) or patient receiving concomitant therapy with presumed activity against COVID-19 (within 24 hours prior to initiation of test treatment).
Non-stratified randomization with a 1:1 ratio of a 5-day intravenous (IV) remdesivir group to a 10-day IV remdesivir group. First dose of 200 mg and then a dose of 100 mg on subsequent days.
Primary endpoint: clinical status at D14, assessed on a 7-point ordinal scale (1: deceased; 2: invasive mechanical ventilation or ECMO; 3: non-invasive ventilation or intense oxygen therapy; 4: mild oxygen therapy; 5: not requiring oxygen but receiving continuous medical care (Covid-19 or non-Covid-19 related); 6: inpatient, not requiring supplemental oxygen or continuous medical care (other than as specified in the remitting protocol); 7: non-hospitalized).
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