1. Patients hospitalized with COVID-19 receiving at least one dose of molnupiravir did not show reduced mortality compared to patients receiving placebo treatment.
2. Molnupiravir was not associated with any dose-limiting side effects.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Molnupiravir is a small molecule that interferes with the viral genome replication process in RNA viruses and has shown efficacy against SARS-CoV-2 and relevant variants of concern in animal models. Molnupiravir has also shown promise in improving clinical outcomes in non-hospitalized patients with COVID-19; however, its impact on hospitalized patients is unknown. In this phase 2 clinical trial, named the MOVe-OUT trial, adult patients hospitalized due to COVID-19 were randomized to receive either 200, 400, or 800mg of molnupiravir by oral administration or placebo treatment. The primary endpoints of interest were safety as measured by adverse side-effects and efficacy as measured by sustained recovery from the hospital after 29 days. Secondary endpoints analyzed all-cause mortality. For safety, the study found that the rates of adverse events were similar across all experimental groups suggesting that molnupiravir was not associated with adverse side effects. For efficacy, all experimental groups also had a similar median time to sustained recovery nor in all-cause mortality, suggesting that molnupiravir was unable to improve clinical outcomes in these COVID-19 patients. Overall, this study found that while molnupiravir did not cause dose-dependent adverse events in patients hospitalized with COVID-19 but was also unable to demonstrate clinical benefit in these patients. The results of this study are limited by the timing of molnupiravir administration as treatment was given at the peak of symptom onset causing hospitalization, earlier therapeutic intervention may be required to detect clinical benefit.
Click to read the study in NEJM Evidence
Relevant Reading: Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
In-Depth [randomized controlled trial]: In this multi-center, phase 2 randomized control trial named the MOVe-OUT trial, 304 patients hospitalized with laboratory-confirmed SARS-CoV-2 were randomized to receive either 200, 400, or 800mg of molnupiravir by oral administration twice daily for 5 days, or placebo treatment. The study excluded patients in a critical condition caused by COVID-19, requiring ventilation, who were immunocompromised, or was not expected to have a clinical response to treatment. Concurrent treatment with standard-of-care remdesivir or glucocorticoids was permitted. The primary measured endpoints were safety as measured by the rate of adverse events, and efficacy as measured by sustained recovery (alive and ready for discharge) from hospitalization by the end of the study. For secondary endpoints, patients were graded for all-cause mortality on the World Health Organization (WHO) Clinical Progression Scale analyzing infection, pulmonary score, oxygen requirements, and urgency for clinical review. Levels of SARS-CoV-2 were also assessed by PCR over the course of hospital stay. The study found no differences in the rate of adverse events between all groups with 55.5% of molnupiravir-treated patients reporting an adverse event and 61.3% in patients receiving placebo treatment. A higher number of patients receiving molnupiravir died by the end of the study; however, some of this effect can be attributed to a greater number of mortality risk factors. Across all groups, the median time to sustained recovery was 9 days. All groups receiving molnupiravir showed no treatment effect with recovery rates between 81.5% and 85.2%, compared to the placebo with a recovery rate of 84.7%. There were also no differences in the secondary endpoint in all-cause mortality between groups. Moreover, no differences were found in SARS-CoV-2 RNA viral load between groups. Taken together, the data demonstrate that while molnupiravir can safely be orally administered to patients hospitalized with COVID-19 up to 800mg, molnupiravir was unable to demonstrate any clinical benefit in terms of sustained recovery from hospitalization. This study was sponsored by Merck pharmaceuticals.
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