Remdesivir in Adults With Severe COVID-19
- Treatment with IV remdesivir did not improve clinical status or decrease mortality in a study population of adults with COVID-19, most of whom did not require mechanical ventilation.
- Treatment with IV remdesivir did not lead to a decrease in SARS-CoV-2 viral load compared to placebo.
Is treatment with remdesivir of adult patients with severe coronavirus disease 2019 (COVID-19) associated with clinical improvement compared to placebo?
The study was a double-blind, placebo-controlled multicenter trial at 10 hospitals in Hubei, China, which enrolled adults (≥18 years) hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who met the following criteria: <12 days of symptoms, oxygen saturation of ≤94% on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of ≤300 mm Hg, and radiologically confirmed pneumonia. Patients were randomized in a 2:1 ratio to intravenous (IV) remdesivir infusions for up to 10 days or placebo. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomization to the point of a decline of two levels on a 6-point ordinal scale of clinical status (1 = discharged, 2 = hospital admission not requiring oxygen, 3 = requiring oxygen … up to 6 = death) or discharged alive from hospital, whichever came first.
A total of 158 patients were randomized to remdesivir, and 79 to placebo. Study patients had a median age of 65 years and consisted of approximately two thirds male. Hypertension (43%) and diabetes mellitus (23%) were the most common comorbidities. There were more patients with hypertension, diabetes, or coronary artery disease in the remdesivir group compared to placebo. The median time from symptom onset to initiation of treatment was 10 days. The number of patients requiring invasive mechanical ventilation was small: 7% in the remdesivir group and 13% in the placebo arm. Viral load and its change with time did not differ between groups. The time to clinical improvement was not significantly different in the remdesivir arm (21 days) compared to the placebo arm (23 days) in both intention-to-treat and per-protocol populations. Twenty-eight-day mortality was similar between the two groups (14% with remdesivir, 13% with placebo). Twenty-eight (18%) serious adverse events were reported in the remdesivir group and 20 (26%) were reported in the control group. No deaths were attributed to the remdesivir.
IV remdesivir was not associated with clinical improvement or mortality in adult patients with COVID-19.
The main results from this highly anticipated trial of remdesivir in COVID-19 are inconclusive. The study did not reach its target enrollment (n = 453), and its study population was overall less ill, with few patients requiring mechanical ventilation during the disease course. Whether remdesivir would be effective in a patient population with more severe illness cannot be ascertained from this trial. Interestingly, remdesivir did not result in significant reductions in SARS-CoV-2 RNA loads or detectability in upper respiratory tract or sputum specimens for reasons that are unclear, and despite showing strong antiviral effects in preclinical models and adequate concentrations in human plasma. Overall, these findings are in contrast with preliminary results announced concurrently from a National Institutes of Health–sponsored remdesivir clinical trial. We eagerly await the details of that report to better understand the discrepant findings.
Keywords: Coronary Artery Disease, Coronavirus, COVID-19, Diabetes Mellitus, Hypertension, Partial Pressure, Patient Discharge, Pneumonia, Primary Prevention, Respiration, Artificial, SARS Virus, Viral Load
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