Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. 12/25/2022. Butler CC. Lancet.

Reviews prior to this study demonstrated molnupiravir reduction in hospitalization following early treatment of PCR positive patients. The largest randomized clinical trial was the placebo-controlled, phase 3 MOVe-OUT trial of 1,433 unvaccinated outpatients with COVID-19, molnupiravir was associated with a relative reduction of roughly 30% in the primary outcome — hospitalisations and deaths — up to 29 days after randomization. Subsequent reports showed less efficacy. This study PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial enrolling ~25,000 patients assigned randomly in two equal arms from 12/08/2021 to 04/27/2022 to receive either usual care only or usual care + 800 mg molnupiravir orally twice daily for 5 days witin 5 days of PCR Confirmed COVID 19. Eligible people were in the community (ie, not in hospital), aged 50 years or older (or 18 years or older with relevant comorbidities), had COVID-19 symptoms that had started within the previous 5 days, and had had a positive PCR or rapid antigen SARS-CoV-2 test within the past 7 days. The primary outcome was all-cause, non-elective hospital admission or death within 28 days of randomisation. Secondary outcomes included time to self-reported recovery, time to sustained alleviation of symptoms, time to initial reduction of symptom severity, contact with health or social services, hospital assessment without admission, oxygen administration, new household COVID-19 infections, and safety outcomes. Virology studies were also performed. This trial of vaccinated adults at increased risk of an adverse outcome and unwell with confirmed SARS-CoV-2 infection showed that early treatment with molnupiravir did not reduce already low hospital admission or deaths. Their findings suggest that, in a highly vaccinated population at high risk (but not the highest risk) of complications from COVID-19, the avoidance of hospitalization and death is primarily achieved via extensive vaccination. The benefits of molnupiravir in terms of faster time to recovery, reduced contact with general practitioner services, and reduced viral load need to be considered in the context of the prevailing disease, burden on health-care services, drug-acquisition cost, social circumstances, cost-effectiveness, and opportunity costs.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02597-1/fulltext