Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial

Abstract

Background: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease.

Objective: To identify other potential clinical benefits of molnupiravir versus placebo.

Design: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597).

Setting: 107 sites globally.

Participants: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19.

Intervention: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days.

Measurements: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo ₂), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization.

Results: Participants receiving molnupiravir showed faster normalization of CRP and Spo ₂, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants.

Limitations: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2.

Conclusion: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death.

Primary funding source: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Visual Abstract.. Additional Clinical Benefits With Molnupiravir for COVID-19.

In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. This secondary analysis of the MOVe-OUT trial sought to identify other potential clinical benefits of molnupiravir versus placebo.

Appendix Figure.. Participant flow chart.

MITT = modified intention-to-treat. * One placebo recipient was lost to follow-up and was thus not considered to be hospitalized for this analysis.

Figure 1.. Mean change in CRP concentration (top) and Spo ₂ (bottom) through day 29 (safety population).

Error bars represent 95% CIs. CRP = high-sensitivity C-reactive protein; EOT = end of therapy; Spo ₂ = oxygen saturation.

Figure 2.. Respiratory interventions through day 29 in the MITT population (top) and the hospitalized MITT population (bottom).

Error bars represent 95% CIs. Each participant was counted only once according to the highest level of O₂ therapy needed. Respiratory interventions included conventional O₂, HF heated and humidified device, noninvasive MV, and invasive MV. HF = high-flow; MITT = modified intention-to-treat; MV = mechanical ventilation; O₂ = oxygen.

Figure 3.. Acute care visits and COVID-19–related acute care visits through day 29 (MITT population).

95% CIs were based on the Miettinen–Nurminen method, with stratification by randomization strata. MITT = modified intention-to-treat.