23.05.2020
Remdesivir for the Treatment of Covid-19 — Preliminary Report
Therapeutic Transversal
Beigel JH et al
NEJM
Main result
Out of 1,107 eligible patients, the inclusion of 1,063 randomized COVID-19 patients in both arms: remdesivir (541) and placebo (522) with a mean age of 58.9 years and 64.3% male. The groups were comparable in terms of their characteristics.
Preliminary results on 391 treated patients and 340 control patients (132 patients in the remdesivir group and 169 in the placebo group had not recovered and had not completed the follow-up visit at D29).
Patients treated with remdesivir had a significantly shorter recovery time than the placebo group (11 days vs. 15 days, RR=1.47, p<0.001). Efficacy was particularly evident in patients with an initially moderate form. For more severe patients, requiring ventilation, efficacy was not statistically significant (RR between 1.38 and 0.95). An adjusted analysis confirmed these results.
Remdesivir treatment also appears to be significantly effective on clinical improvement between D1 and D15 (OR=1.50, p<0.001). For mortality at D28, there was a mortality rate of 7.1% for remdesivir versus 11.9% for placebo (HR=0.74, 95% CI: 0.50 to 1.10), this difference being however not significant.
The treatment's security seems to be satisfactory, since the authors report 21.1% of adverse events with remdesivir versus 27.0% with placebo, but only 2 events in each group directly attributable to the treatment.
Preliminary results on 391 treated patients and 340 control patients (132 patients in the remdesivir group and 169 in the placebo group had not recovered and had not completed the follow-up visit at D29).
Patients treated with remdesivir had a significantly shorter recovery time than the placebo group (11 days vs. 15 days, RR=1.47, p<0.001). Efficacy was particularly evident in patients with an initially moderate form. For more severe patients, requiring ventilation, efficacy was not statistically significant (RR between 1.38 and 0.95). An adjusted analysis confirmed these results.
Remdesivir treatment also appears to be significantly effective on clinical improvement between D1 and D15 (OR=1.50, p<0.001). For mortality at D28, there was a mortality rate of 7.1% for remdesivir versus 11.9% for placebo (HR=0.74, 95% CI: 0.50 to 1.10), this difference being however not significant.
The treatment's security seems to be satisfactory, since the authors report 21.1% of adverse events with remdesivir versus 27.0% with placebo, but only 2 events in each group directly attributable to the treatment.
Takeaways
The preliminary results of this double-blind randomized controlled trial reveal a significant efficacy of remdesivir compared to placebo on recovery time and clinical improvement, particularly in patients with a moderate form of COVID-19. The effect on mortality has yet to be demonstrated and the overall results have yet to be confirmed by analysis of all the data from this study and other well-conducted trials.
Strength of evidence Moderate
A good quality double-blind randomized controlled study, but :
- Preliminary results with few details in the study methodology regarding the criteria for inclusion of patients or the calculation of the number of subjects needed e.g.
- Change in the main judgment criterion under investigation without explanation of the incidence in terms of statistical power
- No information on the conduct of an Intent to Treat analysis
- No information on the characteristics of the patients actually analyzed in this preliminary study (analysis of all inclusions)
Objectives
Assessing the efficacy and safety of remdesivir in the treatment of COVID-19 infection
Method
Multi-center, multi-national (USA, Europe, and Asia) randomized double-blind controlled therapeutic trial
1:1 Randomization for both arms (remdesivir and placebo) stratified by center and disease severity
Treatment arm: IV Remdesivir at a dosage of 200 mg at D1, then 100 mg per day from D2 to D10 or until discharge from hospital versus placebo arm = saline of equal volume and same route of administration in a double-blind fashion.
Inclusion of SARS-CoV-2 infected patients in hospital, followed by management according to current recommendations and assessment of patients from D1 to D29 according to the NEWS score determining clinical status + monitoring of adverse events.
Main Judgement Criterion (MJC) = recovery time defined by the previous score
Secondary endpoints = difference in score between J1 and J15 in both arms (= initially CJP, then change due to literature data indicating a potentially longer disease course)
Statistics: analysis via a stratified log-rank test on the severity of the disease, then adjustment on the initial score and interaction tests carried out. An interim analysis planned by the study's monitoring committee was carried out when the inclusions were completed but the follow-up of some patients was still ongoing. In view of the good results, these preliminary results were then sent for publication and patients were then given the opportunity to request a group change from placebo to remdesivir.
1:1 Randomization for both arms (remdesivir and placebo) stratified by center and disease severity
Treatment arm: IV Remdesivir at a dosage of 200 mg at D1, then 100 mg per day from D2 to D10 or until discharge from hospital versus placebo arm = saline of equal volume and same route of administration in a double-blind fashion.
Inclusion of SARS-CoV-2 infected patients in hospital, followed by management according to current recommendations and assessment of patients from D1 to D29 according to the NEWS score determining clinical status + monitoring of adverse events.
Main Judgement Criterion (MJC) = recovery time defined by the previous score
Secondary endpoints = difference in score between J1 and J15 in both arms (= initially CJP, then change due to literature data indicating a potentially longer disease course)
Statistics: analysis via a stratified log-rank test on the severity of the disease, then adjustment on the initial score and interaction tests carried out. An interim analysis planned by the study's monitoring committee was carried out when the inclusions were completed but the follow-up of some patients was still ongoing. In view of the good results, these preliminary results were then sent for publication and patients were then given the opportunity to request a group change from placebo to remdesivir.
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