A randomized controlled trial with more than 25,000 participants suggests that use of the antiviral molnupiranir does not reduce deaths or hospital admissions among patients with COVID-19 infection who are vaccinated and are at increased risk of mortality. However, patients taking molnupiravir recovered more quickly (on average, 4.2 days faster) compared to patients in the trial’s control group.
Previous studies among unvaccinated patients suggested that molnupiravir could help prevent hospital admission, but this study provides new evidence that policymakers should consider when formulating winter COVID-19 strategies.
Molnupiravir (taken at a dose of 800 mg twice daily for five days) does not reduce hospital admissions or deaths in vaccinated adults with COVID-19 infection who are at increased risk of mortality, according to results from a randomized controlled trial , published in The Lancet journal. However, patients treated at home with molnupiravir recovered faster than the control group.
Previous studies suggested that molnupiravir is effective in reducing hospital admissions in patients with mild to moderate COVID-19 and the WHO recommends its use for patients at highest risk of hospital admission. However, so far studies have been carried out in largely unvaccinated populations and before the appearance of the omicron variant. This new trial was carried out in a largely vaccinated population where the majority of COVID-19 infections were the omicron variant and is therefore more applicable to the current situation in the UK.
Molnupiravir is one of the most expensive antivirals used to treat COVID-19, with a seven-day course costing around $700 in the US, equivalent to £577 (compared to around $530/ £437 for a five-day Paxlovid course). Molnuvirapir was shipped directly to trial participants and could be taken orally at home.
“Although this trial found no benefit from molnupiravir treatment in its primary outcome, which hypothesized that molnupiravir treatment for vaccinated and at-risk patients would reduce the likelihood of hospitalization or death, the trial suggests that this treatment may have other benefits.” benefits when used. to treat COVID-19, such as faster recovery time and reduced follow-up with health services. This could help ease the burden on UK health services by treating selected patients at home, at times of high disease burden and pressure on key services. We therefore hope that this new evidence will be useful to policymakers when preparing strategies to control COVID-19 infections during the winter,” says lead author Professor Chris Butler, from the University of Oxford, UK. United.
The study included 25,708 participants aged 18 years and older (average age 57 years) at increased risk of death or hospitalization from COVID-19 infection in healthcare settings across the UK. Patients were considered to be at higher risk of hospitalization or death if they were 50 years or older, or if they were 18 years or older with relevant underlying health conditions. The patients had a confirmed COVID-19 omicron infection and were unwell for five days or less before starting treatment. The results represent the results of patients treated between December 8, 2021 and April 27, 2022, during the peak of the omicron wave in the United Kingdom.
About half of the patients in the trial (12,774 people) received 800 mg of molnupiravir twice a day for five days, taken at home, in addition to standard care. The control half of the trial (12,934 people) received only standard care.
The main objective being investigated was whether molnupiravir reduced the risk of hospitalization or death. Secondary objectives (planned outcome measures that are not as important as the primary outcome but are still of interest in evaluating the effect of an intervention [4]) related to recovery time and symptoms. Patients reported outcomes using an online diary for 28 days of follow-up.
No benefits were seen in hospitalization or death rates between the molnupiravir group and the control group.
In the group treated with molnupiravir there were 105 cases of death or hospitalization (0.8%), while in the control group there were 98 cases of death or hospitalization (0.8%).
Participants receiving molnupiravir reported more favorable outcomes for a variety of secondary outcomes in this study. The average median duration of illness in patients taking molnupiravir was nine days compared to 15 days in the control group. Using a statistical model that accounted for the range of recovery times in both groups, the authors found that patients taking molnupiravir recovered an average of 4.2 days faster compared to patients in the control group.
Furthermore, seven patients in the control group did not achieve recovery within 28 days of follow-up. Modestly fewer patients who were treated with molnupiravir sought additional medical care after the trial (20% of molnupiravir patients compared to 24% of the control group).
“As countries advance their strategies to manage successive waves of COVID-19 infections, the issue of antibiotic resistance must not be forgotten. While it is essential to ensure that patients who are likely to benefit from treatment with antiviral treatments, such as molnuvirapir, receive them; Using antivirals to treat patients who are unlikely to benefit carries the risk of further driving antimicrobial resistance, wasting resources, and exposing people to unnecessary harm. "Therefore, our study contributes to the valuable evidence base on who should not be treated with these precious newly discovered agents, to empower doctors to make decisions based on solid evidence when prescribing treatments for COVID-19 infections." says study co-author Professor Ly-Mee Yu, University of Oxford, UK.
The authors caution that the benefits of molnupiravir use should be considered in the context of the burden on healthcare services and cost-effectiveness. Further health and economic analyzes are underway, and participants are still being monitored to determine the effect of molnupiravir treatment for COVID-19 on long-term symptoms. The authors also acknowledge that the open-label design of the trial means they were unable to estimate the positive effect of molnupiravir on symptoms resulting from any placebo effect. However, this limitation is unlikely to affect the trial’s primary outcome of non-elective hospitalization and/or death.
Writing in a linked comment, Professor Michael Kidd, Australian Government Department of Health and Aged Care, Canberra, Australia, who was not involved in the study, says: "Butler and colleagues acknowledge that their findings may be " less applicable." " in people with COVID-19 who are clinically extremely vulnerable. We would go a step further and urge caution when trying to apply the findings of this study to those at highest risk of complications from COVID-19. Although PANORAMIC was not powered for secondary outcomes , there are important policy implications for the study’s secondary endpoints. The trial showed that adding molnupiravir to usual care resulted in faster recovery time and reduced detection and viral load (in a small virology substudy). The shortened and sustained reduction in symptoms, together with the effects on viral clearance, could be an important consideration in high-risk settings, such as nursing homes, in terms of potentially minimizing the spread of infection among people of high risk. “Molnupiravir could also provide benefits to healthcare systems, especially during community surges, by potentially allowing healthcare workers to safely return to work sooner.”
