tetano
Editor, Senior Moderator
N Engl J Med
. 2026 Apr 23;394(16):1583-1594.
doi: 10.1056/NEJMoa2502457.
Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients
Christopher C Butler[SUP] 1 [/SUP], Andrew D Pinto[SUP] 2 3 4 5 [/SUP], Victoria Harris[SUP] 1 [/SUP], Jane Holmes[SUP] 1 [/SUP], Najib M Rahman[SUP] 6 7 8 [/SUP], Lucy Cureton[SUP] 1 [/SUP], Gail Hayward[SUP] 1 [/SUP], Duncan B Richards[SUP] 9 [/SUP], David M Lowe[SUP] 10 [/SUP], Joseph F Standing[SUP] 10 [/SUP], Judith Breuer[SUP] 11 [/SUP], Kerenza Hood[SUP] 12 [/SUP], May Ee Png[SUP] 1 [/SUP], Stavros Petrou[SUP] 1 [/SUP], Jienchi Dorward[SUP] 1 13 [/SUP], Mahendra G Patel[SUP] 1 [/SUP], Nicholas P B Thomas[SUP] 14 15 16 [/SUP], Philip Evans[SUP] 14 17 [/SUP], Nigel D Hart[SUP] 18 [/SUP], Bhautesh D Jani[SUP] 19 [/SUP], Banafshe Hosseini[SUP] 2 4 5 [/SUP], Srinivas Murthy[SUP] 20 [/SUP], Kerry McBrien[SUP] 21 22 [/SUP], Amanda Condon[SUP] 23 [/SUP], Emily G McDonald[SUP] 24 [/SUP], Peter Daley[SUP] 25 [/SUP], Michelle Greiver[SUP] 4 26 [/SUP], Bruno R da Costa[SUP] 5 27 [/SUP], Peter Selby[SUP] 4 5 [/SUP], Peter Jüni[SUP] 5 27 [/SUP], Todd C Lee[SUP] 24 [/SUP], Haolun Shi[SUP] 28 [/SUP], Michelle A Detry[SUP] 29 [/SUP], Christina T Saunders[SUP] 29 [/SUP], Mark Fitzgerald[SUP] 29 [/SUP], Nicholas S Berry[SUP] 29 [/SUP], Benjamin R Saville[SUP] 29 30 [/SUP], Saye H Khoo[SUP] 31 [/SUP], Jonathan S Nguyen-Van-Tam[SUP] 32 [/SUP], F D Richard Hobbs[SUP] 1 [/SUP], Ly-Mee Yu[SUP] 1 [/SUP], Paul Little[SUP] 33 [/SUP]; PANORAMIC Trial and CanTreatCOVID Trial Collaborative Groups
Collaborators, Affiliations
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.).
. 2026 Apr 23;394(16):1583-1594.
doi: 10.1056/NEJMoa2502457.
Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients
Christopher C Butler[SUP] 1 [/SUP], Andrew D Pinto[SUP] 2 3 4 5 [/SUP], Victoria Harris[SUP] 1 [/SUP], Jane Holmes[SUP] 1 [/SUP], Najib M Rahman[SUP] 6 7 8 [/SUP], Lucy Cureton[SUP] 1 [/SUP], Gail Hayward[SUP] 1 [/SUP], Duncan B Richards[SUP] 9 [/SUP], David M Lowe[SUP] 10 [/SUP], Joseph F Standing[SUP] 10 [/SUP], Judith Breuer[SUP] 11 [/SUP], Kerenza Hood[SUP] 12 [/SUP], May Ee Png[SUP] 1 [/SUP], Stavros Petrou[SUP] 1 [/SUP], Jienchi Dorward[SUP] 1 13 [/SUP], Mahendra G Patel[SUP] 1 [/SUP], Nicholas P B Thomas[SUP] 14 15 16 [/SUP], Philip Evans[SUP] 14 17 [/SUP], Nigel D Hart[SUP] 18 [/SUP], Bhautesh D Jani[SUP] 19 [/SUP], Banafshe Hosseini[SUP] 2 4 5 [/SUP], Srinivas Murthy[SUP] 20 [/SUP], Kerry McBrien[SUP] 21 22 [/SUP], Amanda Condon[SUP] 23 [/SUP], Emily G McDonald[SUP] 24 [/SUP], Peter Daley[SUP] 25 [/SUP], Michelle Greiver[SUP] 4 26 [/SUP], Bruno R da Costa[SUP] 5 27 [/SUP], Peter Selby[SUP] 4 5 [/SUP], Peter Jüni[SUP] 5 27 [/SUP], Todd C Lee[SUP] 24 [/SUP], Haolun Shi[SUP] 28 [/SUP], Michelle A Detry[SUP] 29 [/SUP], Christina T Saunders[SUP] 29 [/SUP], Mark Fitzgerald[SUP] 29 [/SUP], Nicholas S Berry[SUP] 29 [/SUP], Benjamin R Saville[SUP] 29 30 [/SUP], Saye H Khoo[SUP] 31 [/SUP], Jonathan S Nguyen-Van-Tam[SUP] 32 [/SUP], F D Richard Hobbs[SUP] 1 [/SUP], Ly-Mee Yu[SUP] 1 [/SUP], Paul Little[SUP] 33 [/SUP]; PANORAMIC Trial and CanTreatCOVID Trial Collaborative Groups
Collaborators, Affiliations
- PMID: 42019019
- DOI: 10.1056/NEJMoa2502457
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.).