DOM COVID-19 Journal Club: Remdesivir in Adults with Severe COVID-19: A Randomised, Double-blind, Placebo-controlled, Multicentre Trial

Background: Remdesivir is a nucleoside analogue prodrug that has been shown to inhibit human and animal coronaviruses in animal models, and SARS-CoV-2 in vitro.

Methods: Randomized, double-blind, placebo-controlled trial in 10 hospitals in Hubei, China [1]. Patients with lab confirmed COVID-19 pneumonia with 12 days or fewer of symptoms were randomized in a 2:1 ratio to IV Remdesivir (200mg on day one, then 100mg up to 10 days) or placebo. Concomitant use of lopinavir-ritonavir, interferons, and corticosteroids was permitted.

Results: 237 patients were randomized, and there was not a statistically significant difference in the primary outcome, which was time to clinical improvement in all patients (improvement in 2 points on an ordinal scale from 1-6, with 1= discharge from hospital, and 6=death). Numerically, patients in the Remdesivir group had faster clinical improvement (21 vs. 23 days), especially in a post-hoc analysis of patients receiving drug within 10 days of symptom onset (18 vs. 23 days), but none of these findings met predefined criteria for statistical significance. There was no difference in mortality (14% vs 13%). There was no difference in viral load by quantitative PCR at various time points. There was no difference in adverse events.

Limitations: The trial had to be stopped early due to low enrollment after control of the outbreak in Wuhan, leading to an under-powered study, and some imbalance between the treatment groups.

Conclusions: Similar to the liponavir-ritonavir trial by the same group [2], this study shows a possible modest benefit of Remdesivir in time to clinical improvement, that is not statistically robust due to an underpowered study. Notably, this is not the NIAID study that led to the emergency use authorization of Remdesivir for COVID-19, and has not yet been published at the time of this writing (5/6/20), but shows a similar signal according to the preliminarily results.

References:

  1. Wang Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 Apr 29.
  2. Cao, B et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe COVID-19. New Engl J Med. 2020 Mar 18. DOI: 10.1056/NEJMoa2001282

The Department of Medicine COVID-19 Journal Club is dedicated to understand and applying data on COVID-19 to inform prevention and management efforts for healthcare workers and patients.

This article by Stephen Halliday, MD, MSCI, assistant professor, Allergy, Pulmonary, and Critical Care Medicine. Reviewed by Nasia Safdar, MD, PhD, professor, Infectious Disease, vice chair for research, Department of Medicine.

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