The LANCET: Published on December, 2022

Oral antivirals have been an important addition to efforts to minimise adverse COVID-19 outcomes in individuals at high risk.

The earlier first trial of molnupiravir showed only a 30% reduction of hospitalisations and deaths with molnupiravir compared with placebo. Subsequent observational studies in Hong Kong, Israel, and Australia have suggested an association between molnupiravir and a reduced risk of death among high-risk people, especially those aged 65 years or older.

However, studies have so far been conducted in largely unvaccinated populations and prior to the emergence of the omicron variant. This new trial was carried out in a majority vaccinated population where most COVID-19 infections were the omicron variant.

PANORAMIC is a UK-based national, multicentre, open-label, multigroup trial of COVID-19 treatments in primary care led by researchers at the University of Oxford. PANORAMIC is the largest randomised trial of novel antiviral agents for COVID-19 so far. 

TAKE HOME MESSAGE:

The PANORAMIC trial was set up to discover new COVID-19 antiviral treatments and identify which groups of higher risk people were most likely to benefit from them.

The study included 25,708 participants over the age of 18 (average age 57 years) with a higher risk of death or hospitalisation from COVID-19 infection from health centres across the UK. The results represent outcomes for patients treated between 8th December 2021 and 27th April 2022, during the peak of the omicron wave in the UK.

Approximately half the patients in the trial (12,774 people) received 800mg molnupiravir twice daily for five days, which was taken at home, in addition to standard care. The control half of the trial (12,934 people) received standard care only.

The main objective under investigation was whether molnupiravir reduced the risk of hospitalisation or death. Secondary objectives related to recovery time and symptoms.

Participants receiving molnupiravir reported more favourable outcomes for a variety of the secondary outcomes in this study. The median average length of illness in patients who took molnupiravir was nine days compared to 15 days in the control group. The authors found that patients taking molnupiravir recovered an average of 4.2 days quicker compared to patients in the control group.

Compared with the usual care group, participants in the molnupiravir plus usual group more often reported early sustained recovery, higher self-rated wellness, reduced time to sustained recovery, reduced time to alleviation of all symptoms (and each symptom, reduced time to sustained alleviation of all symptoms, reduced time to reduction of symptom severity, fewer moderate or severe symptoms at days 7, 14, and 28, and less contact with general practitioners.

In PANORAMIC, molnupiravir was associated with faster alleviation of fever, cough, fatigue, and feeling generally unwell, and shortened time to self-reported recovery. 

The shortened and sustained symptom reduction, together with the effects on viral clearance, could be an important consideration in high-risk settings, such as care homes, in terms of potentially minimising the spread of infection among high-risk people. Molnupiravir might also provide benefits to health-care systems, especially during community surges, by potentially allowing health workers to return safely to work sooner.

Serious adverse events were reported for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. No serious adverse events that were definitely related to the intervention were reported.

CONCLUSIONS

The study provides strong evidence that Molnupiravir (taken as an 800mg dose twice daily for five days) does not reduce hospital admissions or deaths in vaccinated adults with COVID-19 infection who are at higher risk of mortality.

However, the patients treated at home with molnupiravir recovered quicker compared to the control group. The trial showed that the addition of molnupiravir to usual care resulted in faster time to recovery and reduced viral detection and load.

The study reinforces the ongoing importance of the COVID vaccination programme in reducing death and hospitalisation.