Evidence map›Paper›PMID 42019019›Full record

Trial reportThe New England journal of medicine2026

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

Christopher C Butler, Andrew D Pinto, Victoria Harris, Jane Holmes, Najib M Rahman, Lucy Cureton, Gail Hayward, Duncan B Richards, David M Lowe, Joseph F Standing and 33 more

Registry-linked trialAbstract readClinical Trial, Phase IIIEquivalence TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05614349 (Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings), which is not on this map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05614349 phase3active not recruitingnot on this map

Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings

TypeinterventionalSponsorUnity Health TorontoRan2023 to 2025Enrolled797ConditionsCOVID-19ArmsPaxlovid, Antioxidant
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors.

Christopher C ButlerNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-0102-3453
Andrew D PintoUpstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto.
Victoria HarrisNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Jane HolmesNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Najib M RahmanRespiratory Trials Unit, Nuffield, Department of Medicine, University of Oxford, Oxford, United Kingdom.
Lucy CuretonNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Gail HaywardNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Duncan B RichardsDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
David M LoweInstitute of Immunity and Transplantation, University College London, London.
Joseph F StandingInstitute of Immunity and Transplantation, University College London, London.
Judith BreuerInfection, Inflammation and Immunology, UCL Great Ormond Street Institute of Child Health, London.
Kerenza HoodCentre for Trials Research, Cardiff University, Cardiff, United Kingdom.
May Ee PngNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Stavros PetrouNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Jienchi DorwardNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-6072-1430
Mahendra G PatelNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Nicholas P B ThomasNational Institute Health and Care Research Delivery Network, London.
Philip EvansNational Institute Health and Care Research Delivery Network, London.
Nigel D HartSchool of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, United Kingdom.
Bhautesh D JaniGeneral Practice and Primary Care, School of Health and Wellbeing, MVLS, University of Glasgow, Glasgow, United Kingdom.
Banafshe HosseiniUpstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto.
Srinivas MurthyFaculty of Medicine, University of British Columbia, Vancouver, Canada.
Kerry McBrienDepartment of Family Medicine, University of Calgary, Calgary, AB, Canada.
Amanda CondonDepartment of Family Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Emily G McDonaldDepartment of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal.
Peter DaleyMemorial University of Newfoundland, St. John's, Canada.
Michelle GreiverDepartment of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto.
Bruno R da CostaDalla Lana School of Public Health, University of Toronto, Toronto.
Peter SelbyDepartment of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto.ORCID 0000-0001-5401-2996
Peter JüniDalla Lana School of Public Health, University of Toronto, Toronto.
Todd C LeeDepartment of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal.ORCID 0000-0002-2267-4239
Haolun ShiDepartment of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC, Canada.
Michelle A DetryBerry Consultants, Austin, TX.ORCID 0000-0002-2794-1439
Christina T SaundersBerry Consultants, Austin, TX.ORCID 0000-0003-4325-9568
Mark FitzgeraldBerry Consultants, Austin, TX.
Nicholas S BerryBerry Consultants, Austin, TX.
Benjamin R SavilleBerry Consultants, Austin, TX.
Saye H KhooCentre for Experimental Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Jonathan S Nguyen-Van-TamLifespan and Population Health Unit, University of Nottingham School of Medicine, Nottingham, United Kingdom.
F D Richard HobbsNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Ly-Mee YuNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
Paul LittlePrimary Care Research Centre, University of Southampton, Southampton, United Kingdom.
PANORAMIC Trial and CanTreatCOVID Trial Collaborative Groups

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNirmatrelvir-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.

methodsIn 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.

resultsFrom 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.

conclusionsIn 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.).

Indexed as

Antiviral AgentsCOVID-19COVID-19 Drug TreatmentRitonavirAdministration, OralAdolescentAdultAgedAged, 80 and overAzabicyclo CompoundsCOVID-19 VaccinesDrug CombinationsFemaleHospitalizationHumansMaleAntiviral AgentsAzabicyclo CompoundsCOVID-19 VaccinesDrug Combinationsnirmatrelvir and ritonavir drug combinationPyrrolidinonesRitonavir

Identifiers

PMID42019019
PMCPMC7619176

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.