Summary of COVID-19 molnupiravir studies
Studies
Meta Analysis
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PANORAMIC virology-sub-study showing increased viral persistence with molnupiravir treatment. Molnupiravir 800mg twice daily for 5 days led to faster initial viral decline but 86% still had detectable virus by day 5. By day 14, molnupiravir was associated with significantly higher proportions with detectable virus and lower anti-spike antibodies compared to usual care. Serial genome sequencing revealed substantially increased mutagenesis with molnupiravir. Viable virus was cultured from samples up to 9 days post-treatment.
Feb 2024, Nature Communications, https://www.nature.com/articles/s41467-024-45641-0, https://c19p.org/standing
Very small early terminated RCT with 8 molnupiravir and 17 placebo patients showing worse recovery with molnupiravir, without statistical significance.
Nov 2023, BJGP Open, http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109, https://c19p.org/tare
RCT 304 hospitalized patients, 218 treated with molnupiravir, showing no significant differences. MOVe-IN MK-4482-001. NCT04575584.
Dec 2021, NEJM Evidence, https://evidence.nejm.org/pb-assets/evidence-site/content/EVIDoa2100044.pdf, https://c19p.org/arribas
Retrospective 113 lung transplant recipients with mild-to-moderate COVID-19 showing higher mortality with remdesivir and molnupiravir in unadjusted analysis, with statistical significance for remdesivir. mAb PrEP and treatment and the dominant variant favored molnupiravir compared with the control group, however they favored the control group compared with remdesivir.
Jul 2024, Frontiers in Transplantation, https://www.frontiersin.org/articles/10.3389/frtra.2024.1408289/full, https://c19p.org/razia
324 patient molnupiravir late treatment study: 53% higher mortality (p=0.22).
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3
Dose and safety study of molnupiravir with 18 participants, finding no serious adverse events in short-term followup. There was no significant difference in clinical outcomes. NCT04746183.
Aug 2021, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkab318/6358705, https://c19p.org/khoo
Retrospective study of 78 hospitalized COVID-19 patients in Turkey showing no significant difference in mortality or discharge rates with molnupiravir treatment.
Mar 2024, Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, http://dergipark.org.tr/tr/doi/10.34087/cbusbed.1423523, https://c19p.org/ozdemir
923 patient molnupiravir late treatment RCT: 11% higher mortality (p=0.55), 43% higher ventilation (p=0.59), 9% lower hospital discharge (p=0.46), and 12% improved viral clearance (p<0.0001).
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.
May 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.05.23.24307731v1, https://c19p.org/horby
Retrospective 42 elderly patients in China showing faster viral clearance with molnupiravir.
Oct 2022, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-022-00716-7, https://c19p.org/liu5
Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Mar 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281915, https://c19p.org/goodwinm
Propensity score weighted retrospective of 93,883 outpatients in Hong Kong, 5,808 treated with molnupiravir and 4,921 treated with paxlovid, showing higher hospitalization and higher combined mortality/mechanical ventilation/ICU admission with molnupiravir, without statistical significance; and lower hospitalization and combined mortality/mechanical ventilation/ICU admission with paxlovid, statistically significant only for hospitalization.
May 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac687/6678124, https://c19p.org/yip
6,020 patient molnupiravir early treatment study: 100% higher combined mortality/hospitalization (p=0.005).
Retrospective 3,331 sotrovimab and 2,689 molnupiravir patients in the UK, showing higher risk of combined hospitalization/death with molnupiravir.
Nov 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071932, https://c19p.org/zheng4
Retrospective 442 patients in the UK treated with molnupiravir, and 222 eligible but declining treatment, showing no significant difference in hospitalization. No group details are provided and the results are subject to confounding by indication.
Oct 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac527/6750023, https://c19p.org/brown2
Retrospective 65,010 veterans in the USA, showing no significant difference in hospitalization/death with molnupiravir treatment. 1,729 patients received molnupiravir. Authors emulate a target trial closely matching the MOVe-OUT RCT and using 1,459 matched pairs.
Jun 2023, The J. Infectious Diseases, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad195/7187858, https://c19p.org/butt
Retrospective 218 COVID+ lung transplant patients in Germany, showing no significant difference in severe cases with early molnupiravir use.
Sep 2022, Infection, https://link.springer.com/10.1007/s15010-022-01914-8, https://c19p.org/kneidinger
68,640 patient molnupiravir early treatment study: 9% higher combined mortality/hospitalization (p=0.28).
OpenSAFELY retrospective 75,048 outpatients in the UK, using the clone-censor-weight approach to address immortal time bias, showing no significant difference in combined mortality/hospitalization with molnupiravir treatment.
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.12.23289914, https://c19p.org/tazare
5,638 patient molnupiravir early treatment study: 285% higher combined mortality/hospitalization (p=0.004).
OpenSAFELY retrospective 5,638 outpatients in the UK, showing significantly higher hospitalization/death for molnupiravir compared with paxlovid.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.20.23284849, https://c19p.org/zheng5m
Retrospective 294 consecutive patients in Japan, showing higher risk of hospitalization/death with molnupiravir, without statistical significance.
Jan 2023, Research Square, https://www.researchsquare.com/article/rs-2451986/v1, https://c19p.org/inaba
Retrospective 1,921 patients in Japan, showing lower progression with molnupiravir use.
Oct 2022, Clinical and Experimental Medicine, https://link.springer.com/10.1007/s10238-022-00949-3, https://c19p.org/suzuki2
Retrospective 112,380 high-risk patients in the USA, showing significantly higher acute or long-term care admission at 180 days with molnupiravir treatment, and no significant difference for other outcomes. The title and headers of Table S14 are conflicting but the data appears to match be title.
Dec 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.12.05.22283134, https://c19p.org/bajemam
261,706 patient molnupiravir long COVID study: 4% lower PASC (p=0.001).
Retrospective 8,089 molnupiravir patients in the USA showing a small reduction in long COVID with treatment. Confounding is likely significant as below, and may eliminate the benefit. Results specific to the COVID-19 code should be closer to the actual efficacy due to likely lower average severity of the additional treatment patients included based on home tests.
Oct 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2811092, https://c19p.org/fung2
Trial CTRI/2021/08/035424 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Oct 2021, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/aurobindo-pharma-stop-molnupiravir-trial-moderate-covid-19-patients-2021-10-08/, https://c19p.org/mp5424
Trial CTRI/2021/05/033864 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Oct 2021, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/aurobindo-pharma-stop-molnupiravir-trial-moderate-covid-19-patients-2021-10-08/, https://c19p.org/mp3864
Target trial emulation retrospective with 16,495 patients in Hong Kong, showing lower mortality with molnupiravir, but no significant difference for ventilation and ICU admission. See also [acpjournals.org], [acpjournals.org].
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M22-3057, https://c19p.org/wan2
PSM retrospective 2,661 molnupiravir patients in Israel, showing lower mortality and severe COVID-19, without statistical significance. Significant benefit was seen in some subgroups, and significant harm was seen in the <75 subgroup.
Sep 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac781/6708264, https://c19p.org/najjardebbiny2
Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventilatory support. Notably, there is no estimated benefit for ventilatory support, the outcome most directly related to severe COVID-19. The very large difference in vaccine uptake suggests major confounding issues, for example treatment decisions based on vaccine uptake, or confounding by time where control patients are more likely from earlier periods with lower vaccine uptake, which may also correspond to more dangerous variants.
Feb 2024, Kidney Int. Reports, https://www.sciencedirect.com/science/article/pii/S2468024924000986, https://c19p.org/cheng4
Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with molnupiravir treatment.
Feb 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323001172, https://c19p.org/wanm
Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Aug 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae180/7733454, https://c19p.org/lai2
Retrospective 590 patients in Poland, 203 treated with mulnupiravir, showing lower mortality with treatment.
Jul 2022, Pharmacological Reports, https://link.springer.com/10.1007/s43440-022-00408-6, https://c19p.org/flisiak2
PEP RCT 1,527 patients showing lower COVID-19 cases with molnupiravir, without statistical significance.
Sep 2023, J. Infection, https://www.journalofinfection.com/article/S0163-4453(23)00500-5/fulltext, https://c19p.org/alpizar
25,054 patient molnupiravir early treatment RCT: 6% higher combined mortality/hospitalization (p=0.69), 7% higher hospitalization (p=0.67), 2% lower transmission (p=0.88), and 22% improved recovery (p<0.0001).
26,411 patient RCT in the UK, showing faster recovery but no significant difference in hospitalization/death or transmission. Improved recovery may be in part due to the open label design with self-reported symptomatic data. Viral load initially declined more quickly, but was higher at 14 days.
Oct 2022, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673622025971, https://c19p.org/butler2
RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570.
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1, https://c19p.org/fischer
5,332 patient molnupiravir early treatment study: 51% lower combined mortality/hospitalization (p=0.008).
Retrospective high risk outpatients in the UK, showing lower hospitalization/death with molnupiravir treatment. Residual confounding is likely with adjustments having no detail on specific comorbidities.
Jan 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323000828, https://c19p.org/evans2m
Retrospective 19,868 patients eligible for molnupiravir treatment in Israel with 1,069 treated, showing lower mortality and hospitalization with treatment for the subgroup of patients ≥65, and higher mortality for patients 40-64. Authors only provide subgroup results.
Sep 2022, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2204919, https://c19p.org/arbel3
RCT 116 mild/moderate COVID-19 patients in China, showing improved viral clearance with treatment.
Jun 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.939573/full, https://c19p.org/zou
54,217 patient molnupiravir early treatment PSM study: 24% lower mortality (p=0.01), 60% lower ventilation (p=0.02), 26% lower ICU admission (p=0.24), and 2% lower hospitalization (p=0.58).
PSM retrospective 1,074,856 outpatients in Hong Kong, showing lower mortality with molnupiravir.
Oct 2022, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673622015860, https://c19p.org/wong5m
3,712 patient molnupiravir early treatment PSM study: 52% lower mortality (p<0.0001), 58% lower ventilation (p=0.06), 40% lower progression (p<0.0001), and 6% shorter hospitalization (p=0.03).
PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with molnupiravir treatment.
May 2022, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309922005072, https://c19p.org/wong3
180 patient molnupiravir early treatment RCT: 89% lower hospitalization (p=0.12), 12% worse recovery (p=0.74), and 23% improved viral clearance (p=0.07).
RCT 90 molnupiravir and 90 placebo patients, showing faster viral clearance with treatment, not reaching the pre-defined threshold for superiority and recommendation as a candidate for large scale evaluation.
Jul 2022, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309922006442, https://c19p.org/khoo2
Interim report on CTRI/2021/06/033992, showing faster viral clearance. Event counts are approximate, the press release only provides percentages.
Jul 2021, Optimus, Press Release, https://theprint.in/ani-press-releases/optimus-announces-interim-clinical-results-from-phase-iii-clinical-trials-of-molnupiravir-conducted-in-india/699993/, https://c19p.org/optimus
RCT 1,220 patients in India, showing lower risk of hospitalization and improved recovery with treatment. CTRI/2021/07/034588.
Feb 2022, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4042673, https://c19p.org/tippabhotla
Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see [web.archive.org].
Dec 2021, New England J. Medicine, http://www.nejm.org/doi/pdf/10.1056/NEJMoa2116044, https://c19p.org/jaykbernal
Interim results for CTRI/2021/05/033739, showing lower mortality and faster recovery.
Jul 2021, Hetero, Press Release, https://www.heteroworld.com/images/Press_Release_Molnupiravir_Interim_Clinical_Results_Final_090721.pdf, https://c19p.org/hetero
RCT 1,218 outpatients in India, showing lower hospitalization, better clinical improvement, and improved viral clearance with molnupiravir.
Nov 2022, Cureus, https://www.cureus.com/articles/118243-efficacy-and-safety-of-molnupiravir-in-mild-covid-19-patients-in-india, https://c19p.org/sinha
1. Standing et al., Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
592 patient molnupiravir early treatment RCT: 103% worse viral clearance (p=0.33).PANORAMIC virology-sub-study showing increased viral persistence with molnupiravir treatment. Molnupiravir 800mg twice daily for 5 days led to faster initial viral decline but 86% still had detectable virus by day 5. By day 14, molnupiravir was associated with significantly higher proportions with detectable virus and lower anti-spike antibodies compared to usual care. Serial genome sequencing revealed substantially increased mutagenesis with molnupiravir. Viable virus was cultured from samples up to 9 days post-treatment.
Feb 2024, Nature Communications, https://www.nature.com/articles/s41467-024-45641-0, https://c19p.org/standing
2. Tare et al., The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice
25 patient molnupiravir early treatment RCT: 83% worse recovery (p=0.36).Very small early terminated RCT with 8 molnupiravir and 17 placebo patients showing worse recovery with molnupiravir, without statistical significance.
Nov 2023, BJGP Open, http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109, https://c19p.org/tare
3. Arribas et al., Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19
291 patient molnupiravir late treatment RCT: 282% higher mortality (p=0.31), 1% improved recovery (p=0.96), and 12% improved viral clearance (p=0.57).RCT 304 hospitalized patients, 218 treated with molnupiravir, showing no significant differences. MOVe-IN MK-4482-001. NCT04575584.
Dec 2021, NEJM Evidence, https://evidence.nejm.org/pb-assets/evidence-site/content/EVIDoa2100044.pdf, https://c19p.org/arribas
4. Razia et al., Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience
83 patient molnupiravir early treatment study: 272% higher mortality (p=0.28) and 28% lower hospitalization (p=0.58).Retrospective 113 lung transplant recipients with mild-to-moderate COVID-19 showing higher mortality with remdesivir and molnupiravir in unadjusted analysis, with statistical significance for remdesivir. mAb PrEP and treatment and the dominant variant favored molnupiravir compared with the control group, however they favored the control group compared with remdesivir.
Jul 2024, Frontiers in Transplantation, https://www.frontiersin.org/articles/10.3389/frtra.2024.1408289/full, https://c19p.org/razia
324 patient molnupiravir late treatment study: 53% higher mortality (p=0.22).
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3
6. Khoo et al., Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study
18 patient molnupiravir early treatment RCT: 33% worse recovery (p=0.63).Dose and safety study of molnupiravir with 18 participants, finding no serious adverse events in short-term followup. There was no significant difference in clinical outcomes. NCT04746183.
Aug 2021, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkab318/6358705, https://c19p.org/khoo
7. Özdemir et al., COVID-19 enfeksi̇yonunda molnupiravi̇r tedavi̇si̇ alan hastalarin değerlendi̇ri̇lmesi̇
78 patient molnupiravir late treatment study: 50% higher mortality (p=1) and no change in ICU admission (p=1).Retrospective study of 78 hospitalized COVID-19 patients in Turkey showing no significant difference in mortality or discharge rates with molnupiravir treatment.
Mar 2024, Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, http://dergipark.org.tr/tr/doi/10.34087/cbusbed.1423523, https://c19p.org/ozdemir
923 patient molnupiravir late treatment RCT: 11% higher mortality (p=0.55), 43% higher ventilation (p=0.59), 9% lower hospital discharge (p=0.46), and 12% improved viral clearance (p<0.0001).
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.
May 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.05.23.24307731v1, https://c19p.org/horby
9. Liu et al., Disease Progression of Hospitalized Elderly Patients with Omicron BA.2 Treated with Molnupiravir
42 patient molnupiravir early treatment study: 18% shorter hospitalization (p=0.14) and 21% faster viral clearance (p=0.1).Retrospective 42 elderly patients in China showing faster viral clearance with molnupiravir.
Oct 2022, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-022-00716-7, https://c19p.org/liu5
10. Goodwin et al., Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
416 patient molnupiravir early treatment study: 110% higher mortality (p=0.47) and 58% lower hospitalization (p=0.7).Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Mar 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281915, https://c19p.org/goodwinm
11. Yip et al., Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients
88,962 patient molnupiravir early treatment study: 12% higher combined mortality/ICU admission (p=0.66) and 17% higher hospitalization (p=0.06).Propensity score weighted retrospective of 93,883 outpatients in Hong Kong, 5,808 treated with molnupiravir and 4,921 treated with paxlovid, showing higher hospitalization and higher combined mortality/mechanical ventilation/ICU admission with molnupiravir, without statistical significance; and lower hospitalization and combined mortality/mechanical ventilation/ICU admission with paxlovid, statistically significant only for hospitalization.
May 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac687/6678124, https://c19p.org/yip
6,020 patient molnupiravir early treatment study: 100% higher combined mortality/hospitalization (p=0.005).
Retrospective 3,331 sotrovimab and 2,689 molnupiravir patients in the UK, showing higher risk of combined hospitalization/death with molnupiravir.
Nov 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071932, https://c19p.org/zheng4
13. Brown et al., Demographics and outcomes of initial phase of COVID-19 Medicines Delivery Units across 4 UK centres during peak B1.1.529 omicron epidemic: a service evaluation
664 patient molnupiravir early treatment study: 101% higher hospitalization (p=0.51).Retrospective 442 patients in the UK treated with molnupiravir, and 222 eligible but declining treatment, showing no significant difference in hospitalization. No group details are provided and the results are subject to confounding by indication.
Oct 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac527/6750023, https://c19p.org/brown2
14. Butt et al., Molnupiravir Use and 30-Day Hospitalizations or Death in Previously Uninfected Non-hospitalized High-risk Population with COVID-19
65,010 patient molnupiravir early treatment study: 9% higher combined mortality/hospitalization (p=0.75).Retrospective 65,010 veterans in the USA, showing no significant difference in hospitalization/death with molnupiravir treatment. 1,729 patients received molnupiravir. Authors emulate a target trial closely matching the MOVe-OUT RCT and using 1,459 matched pairs.
Jun 2023, The J. Infectious Diseases, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad195/7187858, https://c19p.org/butt
15. Kneidinger et al., Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study
218 patient molnupiravir early treatment study: 15% higher severe cases (p=0.71).Retrospective 218 COVID+ lung transplant patients in Germany, showing no significant difference in severe cases with early molnupiravir use.
Sep 2022, Infection, https://link.springer.com/10.1007/s15010-022-01914-8, https://c19p.org/kneidinger
68,640 patient molnupiravir early treatment study: 9% higher combined mortality/hospitalization (p=0.28).
OpenSAFELY retrospective 75,048 outpatients in the UK, using the clone-censor-weight approach to address immortal time bias, showing no significant difference in combined mortality/hospitalization with molnupiravir treatment.
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.12.23289914, https://c19p.org/tazare
5,638 patient molnupiravir early treatment study: 285% higher combined mortality/hospitalization (p=0.004).
OpenSAFELY retrospective 5,638 outpatients in the UK, showing significantly higher hospitalization/death for molnupiravir compared with paxlovid.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.20.23284849, https://c19p.org/zheng5m
18. Inaba et al., Real-world data concerning the efficacy of molnupiravir in patients vaccinated against COVID-19 during the Omicron surge in Japan
294 patient molnupiravir early treatment study: 127% higher combined mortality/hospitalization (p=0.22) and 127% higher hospitalization (p=0.22).Retrospective 294 consecutive patients in Japan, showing higher risk of hospitalization/death with molnupiravir, without statistical significance.
Jan 2023, Research Square, https://www.researchsquare.com/article/rs-2451986/v1, https://c19p.org/inaba
19. Suzuki et al., Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic
920 patient molnupiravir early treatment PSM study: 53% lower progression (p=0.04).Retrospective 1,921 patients in Japan, showing lower progression with molnupiravir use.
Oct 2022, Clinical and Experimental Medicine, https://link.springer.com/10.1007/s10238-022-00949-3, https://c19p.org/suzuki2
20. Bajema et al., Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes
1,794 patient molnupiravir early treatment PSM study: 18% lower mortality (p=0.4), 1% lower ICU admission (p=1), and 30% higher hospitalization (p=0.04).Retrospective 112,380 high-risk patients in the USA, showing significantly higher acute or long-term care admission at 180 days with molnupiravir treatment, and no significant difference for other outcomes. The title and headers of Table S14 are conflicting but the data appears to match be title.
Dec 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.12.05.22283134, https://c19p.org/bajemam
261,706 patient molnupiravir long COVID study: 4% lower PASC (p=0.001).
Retrospective 8,089 molnupiravir patients in the USA showing a small reduction in long COVID with treatment. Confounding is likely significant as below, and may eliminate the benefit. Results specific to the COVID-19 code should be closer to the actual efficacy due to likely lower average severity of the additional treatment patients included based on home tests.
Oct 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2811092, https://c19p.org/fung2
22. Reuters et al., Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19
molnupiravir late treatment RCT: no change in recovery (p=1).Trial CTRI/2021/08/035424 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Oct 2021, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/aurobindo-pharma-stop-molnupiravir-trial-moderate-covid-19-patients-2021-10-08/, https://c19p.org/mp5424
23. Reuters et al., Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19
molnupiravir late treatment RCT: no change in recovery (p=1).Trial CTRI/2021/05/033864 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Oct 2021, Reuters, https://www.reuters.com/business/healthcare-pharmaceuticals/aurobindo-pharma-stop-molnupiravir-trial-moderate-covid-19-patients-2021-10-08/, https://c19p.org/mp3864
24. Wan et al., Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19
16,495 patient molnupiravir late treatment study: 13% lower mortality (p<0.0001), 7% higher ventilation (p=0.49), and 2% higher ICU admission (p=0.9).Target trial emulation retrospective with 16,495 patients in Hong Kong, showing lower mortality with molnupiravir, but no significant difference for ventilation and ICU admission. See also [acpjournals.org], [acpjournals.org].
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M22-3057, https://c19p.org/wan2
25. Najjar-Debbiny et al., Effectiveness of Molnupiravir in High Risk Patients: a Propensity Score Matched Analysis
5,322 patient molnupiravir early treatment PSM study: 19% lower mortality (p=0.48), 17% lower progression (p=0.34), and 25% lower severe cases (p=0.15).PSM retrospective 2,661 molnupiravir patients in Israel, showing lower mortality and severe COVID-19, without statistical significance. Significant benefit was seen in some subgroups, and significant harm was seen in the <75 subgroup.
Sep 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac781/6708264, https://c19p.org/najjardebbiny2
26. Cheng et al., Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19
9,938 patient molnupiravir early treatment study: 15% lower mortality (p=0.003), no change in oxygen therapy (p=1), and 12% lower ICU admission (p=0.52).Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventilatory support. Notably, there is no estimated benefit for ventilatory support, the outcome most directly related to severe COVID-19. The very large difference in vaccine uptake suggests major confounding issues, for example treatment decisions based on vaccine uptake, or confounding by time where control patients are more likely from earlier periods with lower vaccine uptake, which may also correspond to more dangerous variants.
Feb 2024, Kidney Int. Reports, https://www.sciencedirect.com/science/article/pii/S2468024924000986, https://c19p.org/cheng4
27. Wan et al., Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase
23,436 patient molnupiravir late treatment study: 11% lower mortality (p=0.02), 1% lower hospitalization (p=0.76), and 4% higher progression (p=0.18).Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with molnupiravir treatment.
Feb 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323001172, https://c19p.org/wanm
28. Lai et al., Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study
13,642 patient molnupiravir late treatment study: 10% lower mortality (p=0.007).Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Aug 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae180/7733454, https://c19p.org/lai2
29. Flisiak et al., Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance
590 patient molnupiravir early treatment study: 39% lower mortality (p=0.03), 5% lower ventilation (p=1), and 1% longer hospitalization (p=0.97).Retrospective 590 patients in Poland, 203 treated with mulnupiravir, showing lower mortality with treatment.
Jul 2022, Pharmacological Reports, https://link.springer.com/10.1007/s43440-022-00408-6, https://c19p.org/flisiak2
30. Alpizar et al., Molnupiravir for Intra-Household Prevention of COVID-19: the MOVe-AHEAD Randomized, Placebo-Controlled Trial
1,527 patient molnupiravir prophylaxis RCT: 24% fewer symptomatic cases (p=0.06).PEP RCT 1,527 patients showing lower COVID-19 cases with molnupiravir, without statistical significance.
Sep 2023, J. Infection, https://www.journalofinfection.com/article/S0163-4453(23)00500-5/fulltext, https://c19p.org/alpizar
25,054 patient molnupiravir early treatment RCT: 6% higher combined mortality/hospitalization (p=0.69), 7% higher hospitalization (p=0.67), 2% lower transmission (p=0.88), and 22% improved recovery (p<0.0001).
26,411 patient RCT in the UK, showing faster recovery but no significant difference in hospitalization/death or transmission. Improved recovery may be in part due to the open label design with self-reported symptomatic data. Viral load initially declined more quickly, but was higher at 14 days.
Oct 2022, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673622025971, https://c19p.org/butler2
32. Fischer et al., Molnupiravir, an Oral Antiviral Treatment for COVID-19
202 patient molnupiravir early treatment RCT: 77% lower mortality (p=0.31) and 49% improved viral clearance (p=0.12).RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570.
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1, https://c19p.org/fischer
5,332 patient molnupiravir early treatment study: 51% lower combined mortality/hospitalization (p=0.008).
Retrospective high risk outpatients in the UK, showing lower hospitalization/death with molnupiravir treatment. Residual confounding is likely with adjustments having no detail on specific comorbidities.
Jan 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323000828, https://c19p.org/evans2m
34. Arbel et al., Molnupiravir Use and Severe Covid-19 Outcomes During the Omicron Surge
19,868 patient molnupiravir early treatment study: 74% lower mortality (p=0.008) and 45% lower hospitalization (p=0.01).Retrospective 19,868 patients eligible for molnupiravir treatment in Israel with 1,069 treated, showing lower mortality and hospitalization with treatment for the subgroup of patients ≥65, and higher mortality for patients 40-64. Authors only provide subgroup results.
Sep 2022, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2204919, https://c19p.org/arbel3
35. Zou et al., Antiviral Efficacy and Safety of Molnupiravir Against Omicron Variant Infection: A Randomized Controlled Clinical Trial
108 patient molnupiravir early treatment RCT: 29% faster recovery (p=0.5) and 10% faster viral clearance (p=0.009).RCT 116 mild/moderate COVID-19 patients in China, showing improved viral clearance with treatment.
Jun 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.939573/full, https://c19p.org/zou
54,217 patient molnupiravir early treatment PSM study: 24% lower mortality (p=0.01), 60% lower ventilation (p=0.02), 26% lower ICU admission (p=0.24), and 2% lower hospitalization (p=0.58).
PSM retrospective 1,074,856 outpatients in Hong Kong, showing lower mortality with molnupiravir.
Oct 2022, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673622015860, https://c19p.org/wong5m
3,712 patient molnupiravir early treatment PSM study: 52% lower mortality (p<0.0001), 58% lower ventilation (p=0.06), 40% lower progression (p<0.0001), and 6% shorter hospitalization (p=0.03).
PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with molnupiravir treatment.
May 2022, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309922005072, https://c19p.org/wong3
180 patient molnupiravir early treatment RCT: 89% lower hospitalization (p=0.12), 12% worse recovery (p=0.74), and 23% improved viral clearance (p=0.07).
RCT 90 molnupiravir and 90 placebo patients, showing faster viral clearance with treatment, not reaching the pre-defined threshold for superiority and recommendation as a candidate for large scale evaluation.
Jul 2022, The Lancet Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1473309922006442, https://c19p.org/khoo2
39. Optimus et al., Optimus announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India
355 patient molnupiravir early treatment RCT: 58% improved viral clearance (p<0.0001).Interim report on CTRI/2021/06/033992, showing faster viral clearance. Event counts are approximate, the press release only provides percentages.
Jul 2021, Optimus, Press Release, https://theprint.in/ani-press-releases/optimus-announces-interim-clinical-results-from-phase-iii-clinical-trials-of-molnupiravir-conducted-in-india/699993/, https://c19p.org/optimus
40. Tippabhotla et al., Efficacy and Safety of Molnupiravir for the Treatment of Non-Hospitalized Adults With Mild COVID-19: A Randomized, Open-Label, Parallel-Group Phase 3 Trial
1,220 patient molnupiravir early treatment RCT: 46% lower hospitalization (p=0.26), 46% greater improvement (p<0.0001), and 59% improved viral clearance (p<0.0001).RCT 1,220 patients in India, showing lower risk of hospitalization and improved recovery with treatment. CTRI/2021/07/034588.
Feb 2022, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4042673, https://c19p.org/tippabhotla
41. Jayk Bernal et al., Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
1,408 patient molnupiravir early treatment RCT: 89% lower mortality (p=0.01), 30% lower combined mortality/hospitalization (p=0.05), 15% faster recovery (p=0.02), and 4% improved viral clearance (p=0.2).Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see [web.archive.org].
Dec 2021, New England J. Medicine, http://www.nejm.org/doi/pdf/10.1056/NEJMoa2116044, https://c19p.org/jaykbernal
42. Hetero et al., Hetero Announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India
741 patient molnupiravir early treatment RCT: 70% lower hospitalization (p=0.003) and 33% faster recovery (p=0.0001).Interim results for CTRI/2021/05/033739, showing lower mortality and faster recovery.
Jul 2021, Hetero, Press Release, https://www.heteroworld.com/images/Press_Release_Molnupiravir_Interim_Clinical_Results_Final_090721.pdf, https://c19p.org/hetero
43. Sinha et al., Efficacy and Safety of Molnupiravir in Mild COVID-19 Patients in India
1,218 patient molnupiravir early treatment RCT: 65% lower hospitalization (p=0.005), 53% greater improvement (p=0.01), and 48% improved viral clearance (p<0.0001).RCT 1,218 outpatients in India, showing lower hospitalization, better clinical improvement, and improved viral clearance with molnupiravir.
Nov 2022, Cureus, https://www.cureus.com/articles/118243-efficacy-and-safety-of-molnupiravir-in-mild-covid-19-patients-in-india, https://c19p.org/sinha
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