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Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Horby et al., medRxiv, doi:10.1101/2024.05.23.24307731, RECOVERY, NCT04381936
May 2024  
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Mortality, COVID-19 -11% Improvement Relative Risk Mortality, all cause 7% Ventilation -43% Discharge -9% Time to discharge -11% no CI Viral load 12% Molnupiravir  RECOVERY  LATE TREATMENT  RCT Is late treatment with molnupiravir beneficial for COVID-19? RCT 923 patients in multiple countries Higher ventilation with molnupiravir (not stat. sig., p=0.59) c19early.org Horby et al., medRxiv, May 2024 Favorsmolnupiravir Favorscontrol 0 0.5 1 1.5 2+
RECOVERY RCT showing no significant differences in mortality, ventilation, or discharge with either molnupiravir (923 patients) or paxlovid (137 patients). Viral load was improved with treatment but did not translate into clinical benefit, which may in part be due to side effects of treatment.
The treatment delay was notably shorter compared to other treatments in this trial - 4 and 5 days from onset for paxlovid and molnupiravir.
There was an exactly one year delay in publication after completion of recruitment. No press release or results are shown on the trial web site. In contrast, a press release was issued for the HCQ arm on the same day that recruitment ended. The one year delay may be a maximum delay due to EU Clinical Trials registration and associated regulatory requirements for the release of results within 12 months.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.
Study covers molnupiravir and paxlovid.
risk of death, 11.3% higher, RR 1.11, p = 0.55, treatment 57 of 445 (12.8%), control 55 of 478 (11.5%), COVID-19, day 28, Supp. Table 4.
risk of death, 7.0% lower, HR 0.93, p = 0.66, treatment 74 of 445 (16.6%), control 79 of 478 (16.5%), adjusted per study, all cause, multivariable, Cox proportional hazards, day 28.
risk of mechanical ventilation, 42.6% higher, RR 1.43, p = 0.59, treatment 8 of 445 (1.8%), control 6 of 476 (1.3%).
risk of no hospital discharge, 9.1% higher, RR 1.09, p = 0.46, treatment 126 of 445 (28.3%), control 124 of 478 (25.9%).
time to discharge, 11.1% higher, relative time 1.11, treatment 445, control 478.
viral load, 12.0% lower, relative load 0.88, p < 0.001, treatment mean 3.51 (±0.1) n=445, control mean 3.99 (±0.13) n=478.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Horby et al., 24 May 2024, Randomized Controlled Trial, multiple countries, preprint, 39 authors, trial NCT04381936 (history) (RECOVERY).
This PaperMolnupiravirAll
open-label, platform trial
Prof Peter W Horby, Prof Martin, RECOVERY J Landray
doi:10.1101/2024.05.23.24307731
a randomised, controlled,
Declaration of interests The authors have no conflict of interest or financial relationships relevant to the submitted work to disclose. No form of payment was given to anyone to produce the manuscript. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The Nuffield Department of Population Health at the University of Oxford has a staff policy of not accepting honoraria or consultancy fees directly or indirectly from industry (see https://www.ndph.ox.ac.uk/files/about/ndph-independenceof-research-policy-jun-20.pdf). Conflicts of interest No form of payment was given to anyone to produce the manuscript. The Nuffield Department of Population Health at the University of Oxford has a staff policy of not accepting honoraria or consultancy fees directly or indirectly from industry (see -0.68 (-1.29, -0.07) 0.03 RR=Hazard ratio for the outcomes of 28-day mortality and hospital discharge, and risk ratio for the outcome of receipt of invasive mechanical ventilation or death (and its subcomponents). CI=confidence interval. *Analyses exclude those on invasive mechanical ventilation at randomization. †Analyses exclude those on any form of ventilation at randomisation. ‡Analyses restricted to those on invasive mechanical ventilation at randomisation. §Analyses exclude those on haemodialysis or haemofiltration at randomisation.
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Late treatment
is less effective
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