Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial

Khoo, Saye; Fitzgerald, Richard J.; Saunders, Geoffrey K.; Middleton, C.; Ahmad, Shazaad; Edwards, Christopher J; Hadjiyiannakis, Dennis; Walker, Lauren; Lyon, Rebecca; Shaw, Victoria; Mozgunov, Pavel; Periselneris, Jimstan; Woods, Christie; Bullock, Katie; Hale, Colin; Reynolds, Helen; Downs, Nichola; Ewings, Sean; Buadi, Amanda; Cameron, David; Edwards, Thomas; Knox, Emma; Donovan-Banfield, I’ah; Greenhalf, William; Chiong, Justin; Lavelle-Langham, Lara; Jacobs, Michael; Northey, Josh; Painter, Wendy; Holman, Wayne; Lalloo, David G.; Tetlow, Michelle; Hiscox, Julian A.; Jaki, Thomas; Fletcher, Thomas; Griffiths, Gareth; Paton, Nicholas I.; Hayden, Fred; Darbyshire, Janet; Lucas, Amy; Lorch, Ulrika; Freedman, Andrew; Knight, Richard J.; Julious, Stevan; Byrne, Rachel; Atienzar, Ana I Cubas; Jones, Jayne; Williams, Chris; Song, Anna V.; Dixon, Ján; Alexandersson, Anja; Hatchard, Parys; Tilt, Emma; Titman, Andrew; Carracedo, Ale Doce; Gorner, Vatsi Chandran; Davies, Andrea; Woodhouse, Louis; Carlucci, Nicola; Okenyi, Emmanuel; Bula, Marcin; Dodd, Kate; Gibney, Jennifer; Dry, Lesley; Gardner, Zalina Rashid; Sammour, Amin; Cole, Christine L.; Rowland, Tim; Tsakiroglu, Maria; Yip, Vincent; Osanlou, Rostam; Stewart, Anna; Parker, Ben; Turgut, Tolga; Ahmed, Aftab; Starkey, Kay; Subin, Sujamole; Stockdale, Jennifer E.; Herring, Lisa; Baker, Jonathon N.; Oliver, Abigail; Pacurar, Mihaela; Owens, Dan; Munro, Alistair; Babbage, Gavin; Faust, Saul N.; Harvey, Matthew; Pratt, Danny; Nagra, Deepak; Vyas, Aashish

doi:10.1016/s1473-3099(22)00644-2

Cited by 57 publications

(66 citation statements)

References 12 publications

(10 reference statements)

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“…Moreover, in our study we did not find any differences in terms of mortality or risk of progression to respiratory failure between vaccinated or unvaccinated patients treated with molnupiravir. Recently Khoo et al, published data regarding the effect of molnupiravir on virological response by SARS-CoV-2 variant and in vaccinated patients [ 19 ]. In this study viral load reductions during molnupiravir treatment were observed in both vaccinated and unvaccinated individuals [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently Khoo et al, published data regarding the effect of molnupiravir on virological response by SARS-CoV-2 variant and in vaccinated patients [ 19 ]. In this study viral load reductions during molnupiravir treatment were observed in both vaccinated and unvaccinated individuals [ 19 ]. In addition, Khoo and colleagues stated that no participants in the molnupiravir group were hospitalized [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study viral load reductions during molnupiravir treatment were observed in both vaccinated and unvaccinated individuals [ 19 ]. In addition, Khoo and colleagues stated that no participants in the molnupiravir group were hospitalized [ 19 ]. Interestingly Wong and colleagues in their real-life use of molnupiravir showed in the subgroup analyses of study outcomes stratified by age and vaccination status, results comparing molnupiravir use and non-use were significant for reduced risks of all-cause mortality and in-hospital disease progression among patients older than 60 years [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

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Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

et al. 2022

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Real-life experience of molnupiravir treatment is lacking, especially in people hospitalized for underlying diseases not related to COVID-19. We conducted a retrospective analysis regarding molnupiravir therapy in patients with SARS-CoV-2 infection admitted for underlying diseases not associated with COVID-19. Forty-four patients were included. The median age was 79 years (interquartile range [IQR]: 51–93 years), and most males were 57,4%. The median Charlson Comorbidity Index and 4C score were, respectively, 5 (IQR: 3–10) and 9.9 (IQR: 4–12). Moreover, 77.5% of the patients had at least two doses of the anti-SARS-CoV-2 vaccine, although 10.6% had not received any SARS-CoV-2 vaccine. Frequent comorbidities were cardiovascular diseases (68.1%), and diabetes (31.9%), and most admissions were for the acute chronic heart (20.4%) or liver (8.5%) failure. After molnupiravir started, 8 (18.1%) patients developed acute respiratory failure, and five (11.4%) patients died during hospitalisation. Moreover, molnupiravir treatment does not result in a statistically significant change in laboratory markers except for an increase in the monocyte count (p = 0.048, Z = 1.978). Molnupiravir treatment in our analysis was safe and well tolerated. In addition, no patients’ characteristics were found significantly related to hospital mortality or an increase in oxygen support. The efficacy of the molecule remains controversial in large clinical studies, and further studies, including larger populations, are required to fill the gap in this issue.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

et al. 2022

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“…Reporting the phase 2 results from the UK AGILE CST-2 study of molnupiravir for SARS-CoV-2 in The Lancet Infectious Diseases , Saye H Khoo and colleagues 1 present output from a platform trial with public funding that has taken an approach inspired by commercial drug developers. The COVID-19 pandemic exposed our lack of potent oral antivirals and, given the previous two decades of outbreaks of RNA viruses, including SARS-CoV, MERS-CoV, and Ebola virus, one could argue that we should have been better prepared.…”

mentioning

confidence: 99%

“…In the study by Khoo and colleagues, 1 molnupiravir shortened the time to negative PCR compared with placebo (8 days [95% CI 8–9] vs 11 days [10–11]), although the predefined threshold for recommending molnupiravir for further testing was not reached. As half the participants in the study were unvaccinated and the median age of the study cohort was 43 years (IQR 28–55), whether results will be similar in a largely vaccinated, older population remains to be seen.…”

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confidence: 99%

Learning and confirming in publicly funded antiviral trials

Standing

Agyeman²

2023

The Lancet Infectious Diseases

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Clinical efficacy and safety of molnupiravir for nonhospitalized and hospitalized patients with COVID‐19: A systematic review and meta‐analysis of randomized control trials

Huang

Liu

et al. 2023

Journal of Medical Virology

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The efficacy of molnupiravir in treating patients with coronavirus disease 2019 (COVID‐19) has been inconsistent across randomized controlled trials (RCTs). Thus, this meta‐analysis was conducted to clarify the literature. A literature search of electronic databases—PubMed, Embase, and Cochrane Library—was performed to identify relevant articles published up to December 31, 2022. Only RCTs that investigated the clinical efficacy and safety of molnupiravir for patients with COVID‐19 were included. The primary outcome was all‐cause mortality at 28–30 days. This pooled analysis of nine RCTs did not reveal a significant difference in all‐cause mortality between molnupiravir and control groups (risk ratio [RR], 0.43; 95% confidence interval [CI], 0.10–1.77) for overall patients. However, the risks of mortality and hospitalization were lower in the molnupiravir group than in the control group (mortality: RR, 0.28; 95% CI, 0.10–0.79; hospitalization: RR, 0.67; 95% CI, 0.45–0.99) among nonhospitalized patients. In addition, molnupiravir use was associated with a borderline higher virological eradication rate relative to the control (RR, 1.05; 95% CI, 1.00–1.11). Finally, no significant difference in adverse event risk was discovered between the groups (RR, 0.98; 95% CI, 0.89–1.08). The findings reveal the clinical benefits of molnupiravir for nonhospitalized patients with COVID‐19. However, molnupiravir may not improve the clinical outcomes of hospitalized patients. These findings support the recommended use of molnupiravir for treating nonhospitalized patients with COVID‐19 but not for hospitalized patients.

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Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial

Cited by 57 publications

References 12 publications

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

Learning and confirming in publicly funded antiviral trials

Clinical efficacy and safety of molnupiravir for nonhospitalized and hospitalized patients with COVID‐19: A systematic review and meta‐analysis of randomized control trials

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