Treatment with remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.
There are currently no approved treatments or vaccines against coronavirus disease 2019 (COVID-19). A variety of clinical trials have been initiated in order to establish evidence around investigational drugs.
The investigators of a new study published in The Lancet have shared results of a randomized, double-blind, placebo-controlled, multicenter trial of the investigational antiviral remdesivir at 10 hospitals in Hubei, China.
Treatment with remdesivir was not associated with statistically significant clinical benefits in adults with severe COVID-19. While not statistically significant, patients receiving remdesivir did show a faster time to clinical improvement compared to placebo among patients with symptom duration of 10 days or less.
Remdesivir is a nucleoside analogue prodrug which has inhibited human coronaviruses in vitro. The experimental antiviral was developed to treat Ebola, and also inhibits Middle East respiratory syndrome, SARS-CoV-1, and SARS-CoV-2 replication in animal models.
Participants in the recent study were adults aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection in Hubei, China.
Eligible patients needed to be enrolled within 12 days or less of symptom onset, with oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia.
The patients were randomly assigned in a 2:1 ratio to 200 mg of remdesivir on day 1 followed by 100 mg from days 2-10, via singular daily intravenous infusions, or to the same volume of placebo infusions. Eligibility allowed for simultaneous use of lopinavir-ritonavir, interferons, and corticosteroids.
The investigators sought to measure time to clinical improvement from the start of treatment until day 28 after randomization. The study took place between February 6 and March 12, 2020.
A total of 237 patients were enrolled, with 158 assigned to the remdesivir group and 79 to the placebo group. There was a patient in the placebo group who withdrew after randomization who is not included in the intention-to-treat analysis.
Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% confidence interval 0.87—1.75]).
Adverse events were reported in 102 (66%) of 155 remdesivir recipients compared with 50 (64%) of 78 placebo recipients. Remdesivir was stopped early due to adverse events in 18 (12%) patients compared with 4 (5%) patients who stopped placebo early.
While not statistically significant, participants who received remdesivir had a faster time to clinical improvement compared with participants receiving placebo (hazard ratio 1·52 [0.95—2.43]).
There were several limitations to the study, including initiation of remdesivir treatment late in the disease course of participants.
The authors concluded that their results would have to be replicated in larger trials. If remdesivir turns out to be more effective than these data suggest, it may be possible to greatly expand the world supply as a recent study showed similar improvement in clinical outcome between 5- and 10-day dosage durations.
Anthony Fauci, MD, director of the National Institutes of Allergy and Infectious Diseases, said Wednesday that the National Institutes of Health trial of remdesivir was likely to herald "quite good news" and called remdesivir a "drug that can block this virus."