The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial has found no significant benefit of treatment with either molnupiravir or Paxlovid (nirmatrelvir-ritonavir) in patients admitted to hospital with COVID-19. The results of these evaluations have been published on medRxiv and will be submitted to a peer-reviewed medical journal.
Both oral antiviral drugs been shown to reduce the risk of hospitalisation in patients with early infection but had not been evaluated adequately in patients hospitalised with severe disease. It had been proposed that these drugs, given alone or used in combination with other antivirals, could improve outcomes for hospitalised patients.
Between 24 January 2022 and 24 May 2023, 923 patients were recruited to the molnupiravir comparison, with 445 patients allocated to receive molnupiravir and 478 patients allocated to receive usual care alone. 137 patients were recruited to the Paxlovid comparison, with 68 patients allocated to receive Paxlovid and 69 allocated to receive usual care alone.
More than three quarters of the participants in both evaluations were vaccinated and more than two thirds of the participants were receiving other antiviral treatments. Recruitment to these two treatment evaluations ended in May 2023 due to low numbers of participants.
The primary outcome measure was death from any cause within 28 days of randomisation. The two secondary outcomes were the likelihood of being discharged from hospital within 28 days of randomisation, and the likelihood of progressing to invasive mechanical ventilation or death.
Key findings:
- At 28 days after randomisation, there was no evidence that treatment with either molnupiravir or Paxlovid reduced mortality compared to usual care alone;
- In the molnupiravir comparison, 74 (17%) patients in the molnupiravir group died compared with 79 (17%) patients in the usual care group;
- In the Paxlovid comparison, 13 (19%) patients in the Paxlovid group died, compared with 13 (19%) in the usual care group;
- Neither treatment was associated with a significant difference in the duration of hospitalisation or the risk of progressing to invasive ventilation or death.
Dr Leon Peto, Senior Clinical Research Fellow at Oxford Population Health said ‘Unfortunately neither of the treatments we tested showed any evidence of benefit. Severe COVID-19 is thankfully much rarer now than it was in 2020-21, but this also means we didn’t recruit enough patients to rule out a small benefit of either treatment, or a benefit in particular groups, such as those with immune problems. However, our results do not support the routine use of molnupiravir or Paxlovid in patients admitted to hospital with COVID-19. We are grateful to all of the patients who took part in these evaluations, and to the many collaborating doctors, nurses, pharmacists, and research staff who worked on the trial.’
The RECOVERY trial was supported by grants to the University of Oxford from the National Institute for Health and Care Research, UK Research and Innovation, and Wellcome. The decision to add molnupiravir and Paxlovid to the trial was made by the University of Oxford researchers leading the trial and the Trial Steering Committee in conjunction with the Chief Medical Officer, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel. Molnupiravir and Paxlovid were supplied by the UK Government in the UK, and bought from commercial suppliers in Nepal and Indonesia. The trial continues to evaluate other treatments for patients hospitalised with influenza or community-acquired pneumonia, funded by Flu Lab.