Lancet Publishes Chinese Clinical Trial of Remdesivir Showing No Significant Efficacy in Severe COVID-19 Patients

On the evening of April 29 (local time), The Lancet officially published online the first global randomized, double-blind, placebo-controlled, multicenter clinical trial of remdesivir conducted in China.

The results showed that, compared with placebo, treatment with the antiviral drug remdesivir in critically ill hospitalized patients did not accelerate recovery or reduce mortality among patients with COVID-19.

Trial Results: No statistically significant difference in time to clinical improvement

The study found no statistically significant difference in the time to clinical improvement between the remdesivir group and the placebo group. The mean time to clinical improvement was 21 days in the remdesivir group and 23 days in the placebo group.

Among patients treated within 10 days of symptom onset, the mean time to clinical improvement was 18 days for those receiving remdesivir and 23 days for those in the placebo group, with no statistically significant difference.

Study Design: Two patient groups, 2:1 allocation

From February 6 to March 12, 2020, the trial enrolled a total of 237 adult hospitalized patients with severe COVID-19.

Excluding one patient who withdrew from the study prior to treatment, 236 eligible patients were randomized into two groups: 158 patients received remdesivir, and 78 patients received placebo.

Regarding inclusion criteria, patients must be enrolled within 12 days after symptom onset, have pneumonia confirmed by chest imaging, and have an oxygen saturation of 94% or lower.

Patients in the remdesivir group received once-daily intravenous infusions of remdesivir: 200 mg on Day 1, followed by 100 mg on Days 2–10.

Patients in the placebo group received placebo infusions for 10 days.

All patients in the trial received standard treatment, including medications such as lopinavir-ritonavir (brand name Kaletra), interferon, and corticosteroids.

Peer Review: "Reasonable Design"

In a commentary published in the same issue of The Lancet, Professor John Norrie of the University of Edinburgh commented: “This study was well designed as a double-blind, placebo-controlled, multicenter randomized trial, and was well conducted, with high protocol adherence and minimal loss to follow-up.”

The Rise and Fall of Remdesivir:

On January 31 local time, The New England Journal of Medicine (NEJM) published online a research paper related to remdesivir, describing the epidemiological and clinical characteristics of the first confirmed case of COVID-19 infection in the United States. The patient initially presented with mild symptoms, which progressed to pneumonia on day 9 of illness. Subsequently, physicians administered remdesivir under the "compassionate use" principle, and the treatment proved effective.

In early February, China took the lead in launching two Phase III clinical trials of remdesivir, employing a randomized, double-blind, placebo-controlled design. These trials targeted patients with severe and mild-to-moderate COVID-19, respectively, to evaluate the efficacy and safety of remdesivir in treating novel coronavirus infection.

Shortly after the launch of clinical trials in China, reports emerged regarding difficulties in recruiting patients for remdesivir trials. On April 11, a public letter from Daniel O’Day, Chairman and Chief Executive Officer of Gilead Sciences, stated that the study in China involving patients with severe disease had been halted due to stalled enrollment, with data pending release. Shortly thereafter, the clinical trial in China targeting patients with mild-to-moderate disease was also terminated early due to enrollment issues.

As the pandemic spread globally, multiple clinical trials were launched internationally.

On April 10 local time, The New England Journal of Medicine published the trial results of remdesivir for the treatment of patients with severe COVID-19 under compassionate use. The trial results showed that among 53 critically ill COVID-19 patients from around the world, 36 patients (68%) experienced symptom relief after receiving remdesivir, but 60% developed side effects.

On April 23, Shenzhen Maternity and Child Healthcare Hospital published a non-peer-reviewed study on bioRxiv. Preliminary findings indicated that remdesivir may exert reproductive toxicity in mice, leading to a significant decrease in total sperm count and motile sperm rate, along with an increased rate of abnormal sperm.

On the evening of April 29, Gilead Sciences also announced the results of clinical trials evaluating 5-day and 10-day remdesivir treatment regimens for severe COVID-19. The results showed that the 10-day and 5-day remdesivir treatment regimens demonstrated similar clinical improvement.

Gilead stated that clinical outcomes varied by region. Excluding Italy, the overall mortality rate on day 14 was 7% in both treatment groups, with 64% of patients showing clinical improvement and 61% being discharged by day 14. Meanwhile, Gilead did not explicitly declare whether the study data represented a success or a failure.

References:

1.https：//doi.org/10.1016/S0140-6736(20)31022-9

2.https：//www.gilead.com/news-and-press/press-room/press-releases/2020/4/gilead-announces-results-from-phase-3-trial-of-investigational-antiviral-remdesivir-in-patients-with-severe-covid-19

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