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, doi:10.1016/S0140-6736(22)02597-1, PANORAMIC, ISRCTN30448031, Oct 2022 (preprint)
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. Longer-term results are from1.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity2-16. Multiple analyses have identified variants potentially created by molnupiravir17-21.
Standard of Care (SOC) for COVID-19 in the study country,
the United Kingdom, is very poor with very low average efficacy for approved treatments22.
The United Kingdom focused on expensive high-profit treatments, approving only one low-cost early treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of early treatment due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments.
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risk of death, 27.1% higher, RR 1.27, p = 0.50, treatment 20 of 11,778 (0.2%), control 15 of 11,230 (0.1%), day 180.
|
|
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.
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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.
|
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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.
|
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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.
|
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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.
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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.
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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.
|
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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.
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risk of viral load, 95.0% higher, RR 1.95, p = 0.01, treatment 21, control 11, all samples, day 14.
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risk of viral load, 92.0% lower, RR 0.08, p < 0.001, treatment 33, control 26, all samples, day 5.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
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Mori et al., Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir, Free Radical Research, doi:10.1080/10715762.2025.2469738.
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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, average treatment delay 3.0 days, trial ISRCTN30448031 (PANORAMIC).
Contact: christopher.butler@phc.ox.
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
The Lancet, doi:10.1016/s0140-6736(22)02597-1
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.
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