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
et al., The Lancet,
26,411 patient RCT in the UK, showing faster recovery but no significant difference in hospitalization/death or transmission. Improved recovery may be in part due to the open label design with self-reported symptomatic data. Viral load initially declined more quickly, but was higher at 14 days.Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See  for analysis of a variant potentially created by molnupiravir.
risk of death, 40.0% lower, RR 0.60, p = 0.51, treatment 3 of 12,529 (0.0%), control 5 of 12,525 (0.0%), NNT 6260, day 28.
risk of death/hospitalization, 6.0% higher, RR 1.06, p = 0.69, treatment 105 of 12,529 (0.8%), control 98 of 12,525 (0.8%), odds ratio converted to relative risk, day 28, primary outcome.
risk of hospitalization, 7.3% higher, RR 1.07, p = 0.67, treatment 103 of 12,529 (0.8%), control 96 of 12,525 (0.8%), day 28.
risk of transmission, 1.9% lower, RR 0.98, p = 0.88, treatment 3,887 of 10,803 (36.0%), control 3,873 of 10,548 (36.7%), NNT 136, odds ratio converted to relative risk.
risk of no sustained recovery, 22.0% lower, RR 0.78, p < 0.001, treatment 3,856 of 12,403 (31.1%), control 4,838 of 12,140 (39.9%), NNT 11.
recovery time, 19.4% lower, relative time 0.81, p < 0.001, treatment 12,403, control 12,140, inverted to make RR<1 favor treatment, sustained recovery.
risk of no first recovery, 30.5% lower, RR 0.70, p < 0.001, treatment 2,675 of 12,403 (21.6%), control 3,766 of 12,140 (31.0%), NNT 11.
recovery time, 26.5% lower, relative time 0.74, p < 0.001, treatment 12,403, control 12,140, inverted to make RR<1 favor treatment, first recovery.
risk of viral load, 95.0% higher, RR 1.95, p = 0.01, treatment 21, control 11, all samples, day 14.
risk of viral load, 92.0% lower, RR 0.08, p < 0.001, treatment 33, control 26, all samples, day 5.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Butler et al., 6 Oct 2022, Randomized Controlled Trial, United Kingdom, peer-reviewed, mean age 56.6, 135 authors, study period 8 December, 2021 - 27 April, 2022, trial ISRCTN30448031
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, platformadaptive randomised controlled trial
Christopher C Butler*, F D Richard Hobbs*, Oghenekome A Gbinigie, Najib M Rahman, Gail Hayward, Duncan B Richards, Jienchi Dorward,
David M Lowe, Joseph F Standing, Judith Breuer, Saye Khoo, Stavros Petrou, Kerenza Hood, Jonathan S Nguyen-Van-Tam, Mahendra G Patel,
Benjamin R Saville, Joe Marion, Emma Ogburn, Julie Allen, Heather Rutter, Nick Francis, Nicholas P B Thomas, Philip Evans, Melissa Dobson,
Tracie-Ann Madden, Jane Holmes, Victoria Harris, May Ee Png, Mark Lown, Oliver van Hecke, Michelle A Detry, Christina T Saunders,
Mark Fitzgerald, Nicholas S Berry, Lazaro Mwandigha, Ushma Galal, Sam Mort, Bhautesh D Jani, Nigel D Hart, Haroon Ahmed, Daniel Butler,
Micheal McKenna, Jem Chalk, Layla Lavallee, Elizabeth Hadley, Lucy Cureton, Magdalena Benysek, Monique Andersson, Maria Coates,
Sarah Barrett, Clare Bateman, Jennifer C Davies, Ivy Raymundo-Wood, Andrew Ustianowski, Andrew Carson-Stevens, Ly-Mee Yu†, Paul Little†,
for the PANORAMIC Trial Collaborative Group‡
Background The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for
SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and
mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital
admissions and deaths associated with COVID-19 in this population.
Methods PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive
randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant
comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants
were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only.
A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs
≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary
for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of
randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned.
This trial is registered with ISRCTN, number 30448031.
Findings Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir
plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately).
12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included
in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of
25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in
105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care
group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There
was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50..
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