Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients

BACKGROUND: Nirmatrelvir-ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir-ritonavir in persons who have been vaccinated, infected naturally, or both is unclear. METHODS: In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)-ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization. RESULTS: From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir-ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir-ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir-ritonavir. Serious adverse events with nirmatrelvir-ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial. CONCLUSIONS: In two open-label trials, nirmatrelvir-ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection. (Funded by the National Institute for Health and Care Research, and others; PANORAMIC ISRCTN number, 2021-005748-31; CanTreatCOVID ClinicalTrials.gov number, NCT05614349.).

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Publication Details

Journal
New England Journal of Medicine
Published
2026-04-22
DOI
https://doi.org/10.1056/nejmoa2502457
Citations
1
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
20.27

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article

Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients

T Lee, Kerenza Hood, Philip Evans, Gail Hayward et al.
1 citations
New England Journal of Medicine
COVID-19 Clinical Research Studies
20.27
article

Oral Nirmatrelvir–Ritonavir for Covid-19 in Higher-Risk Outpatients

T Lee, Kerenza Hood, Philip Evans, Gail Hayward, Andrew Pinto, B Jani, Peter Jüni, Jane Holmes, Najib Mahboob Rahman, Haolun Shi, Benjamin R. Saville, Lucy Cureton, Joseph Frank Standing, Michelle A. Detry, Nicholas Berry, Michelle Greiver, Christina Saunders, May Ee Png, Victoria Harris, Saye Khoo, Nicholas P.B. Thomas, Banafshe Hosseini, Christopher C. Butler, Peter Daley, Peter Selby, Amanda Condon, Judith Breuer, Paul Little, Mark Fitzgerald, F.D. Richard Hobbs, David M. Lowe, Emily G. McDonald, Jonathan S. Nguyen-Van-Tam, Bruno R. da Costa, Duncan B. Richards, Stavros Petrou, Srinivas Murthy, Kerry McBrien, Nigel D. Hart, Ly-Mee Yu, Mahendra G. Patel, Jienchi Dorward
article en
1 citations

Abstract

BACKGROUND: Nirmatrelvir-ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir-ritonavir in persons who have been vaccinated, infected naturally, or both is unclear. METHODS: In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)-ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization. RESULTS: From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir-ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir-ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir-ritonavir. Serious adverse events with nirmatrelvir-ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial. CONCLUSIONS: In two open-label trials, nirmatrelvir-ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection. (Funded by the National Institute for Health and Care Research, and others; PANORAMIC ISRCTN number, 2021-005748-31; CanTreatCOVID ClinicalTrials.gov number, NCT05614349.).

New England Journal of MedicineVol. 394(16)
Queen's University Belfast (GB), St. Michael's Hospital (CA), Memorial University of Newfoundland (CA), 3M (United States) (US), University of British Columbia (CA), University of Nottingham (GB), University of Liverpool (GB), University of Calgary (CA), Simon Fraser University (CA), University of Toronto (CA), Vanderbilt University (US), University of Exeter (GB), University of Cambridge (GB), North York General Hospital (CA), Centre for the AIDS Programme of Research in South Africa (ZA), McGill University Health Centre (CA), Nuffield Orthopaedic Centre (GB), National Institute for Health and Care Excellence (GB), National Institute for Health and Care Research (GB), University of Oxford (GB), Berry & Associates (United States) (US), Health Solutions (Sweden) (SE), NIHR Southampton Biomedical Research Centre (GB), St Michael's Hospital (GB), Science Oxford (GB), St Michael's Hospital (GB), Institute of Infection and Immunity (CA), University of Southampton (GB), University College London (GB), University of Manitoba (CA), McGill University (CA), Royal College of General Practitioners (GB), University of Glasgow (GB), Cardiff University (GB), Orion Corporation (United Kingdom) (GB)
Department of Health and Social Care, Canadian Institutes of Health Research
Zero hunger
Openalex Percentile: Top 1%
COVID-19 Clinical Research Studies
20.27
DOIOpen Access PDFOpenAlex
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