WHO Study Suggests Remdesivir Might Not Be Effective in COVID-19
Is Remedesivir really beneficial for hospitalized patients with COVID-19? A new World Health Organization study contradicts previous research and suggests little or no effectiveness. Find out what the megastudy determined about Remedesivir and three other drugs being used to treat novel coronavirus patients.
OXFORD, UK – The search for effective treatments for COVID-19 continue, as a World Health Organization megastudy found little effectiveness of four re-purposed antiviral drugs, including Remdesivir.
In a preprint on medRxiv, ahead of planned publication in the New England Journal of Medicine, the WHO Solidarity Trial Consortium evaluated Remdesivir, Hydroxychloroquine, Lopinavir (fixed-dose combination with Ritonavir) and Interferon-β1a (mainly subcutaneous; initially with Lopinavir, later not).
University of Oxford-led researchers report that COVID-19 inpatients were randomized equally between whichever study drugs were locally available and open control --up to 5 options: 4 active and local standard-of-care. The study team was focused on in-hospital mortality. Participants include 11,266 adults from 405 hospitals in 30 countries. Of those, 2,750 were allocated Remdesivir, 954 Hydroxychloroquine, 1,411 Lopinavir, 651 Interferon plus Lopinavir, 1412 only Interferon, and 4,088 no study drug. The study notes that compliance was 94-96% midway through treatment, with 2-6% crossover.
Researchers report, 1253 deaths at median day 8, (IQR 4-14), while. Kaplan-Meier 28-day mortality was 12% --39% if already ventilated at randomization, 10% otherwise.
Results indicate that death rate ratios (with 95% CIs and numbers dead/randomized, each drug vs its control) were:
- Remdesivir RR=0.95 (0.81-1.11, p=0.50; 301/2743 active vs 303/2708 control),
- Hydroxychloroquine RR=1.19 (0.89-1.59, p=0.23; 104/947 vs 84/906),
- Lopinavir RR=1.00 (0.79-1.25, p=0.97; 148/1399 vs 146/1372) and
- Interferon RR=1.16 (0.96-1.39, p=0.11; 243/2050 vs 216/2050).
“No study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics), initiation of ventilation or hospitalization duration,” researchers point out.
The authors conclude, “these Remdesivir, Hydroxychloroquine, Lopinavir and Interferon regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir and Interferon and are consistent with meta-analyses of mortality in all major trials.”
The findings were especially surprising for Remdesivir which had shown clinically meaningful benefit in patients with severe COVID-19, although its efficacy was less clear in those hospitalized with more moderate COVID-19-related pneumonia. A report in JAMA described the results of a randomized, open-label, phase 3 trial of that included 584 patients with moderate COVID-19.
In late August, the U.S. Food and Drug Administration broadened the scope of the existing emergency use authorization remdesivir to include treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease.