Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial.

Abstract

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19. This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure. Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 and significantly reduced the number of COVID-19‒related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required ICU admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through Week 24 compared with 15 placebo-treated patients. In addition to reducing COVID-19‒related hospitalization or death from any cause through Day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease. ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202.