{
  "abstract": "Introduction SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.Methods and analysis CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.Ethics and dissemination The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).Trial registration number NCT05614349",
  "authors": [
    {
      "affiliations": [
        "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Banafshe Hosseini"
    },
    {
      "affiliations": [
        "Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Amanda Condon"
    },
    {
      "affiliations": [
        "Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK",
        "Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Bruno R. da Costa"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada",
        "Eastern Regional Health Authority, St. John's, Newfoundland and Labrador, Canada"
      ],
      "name": "Peter Daley"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, North York General Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Michelle Greiver"
    },
    {
      "affiliations": [
        "Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK",
        "Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Peter Jüni"
    },
    {
      "affiliations": [
        "Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada"
      ],
      "name": "Todd C Lee"
    },
    {
      "affiliations": [
        "Department of Family Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada",
        "Department Community Health Sciences, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Kerry McBrien"
    },
    {
      "affiliations": [
        "Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, Quebec, Canada",
        "Division of General Internal Medicine, Department of Medicine, McGill University, Montréal, Quebec, Canada"
      ],
      "name": "Emily G McDonald"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"
      ],
      "name": "Srinivas Murthy"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada",
        "Addiction Programs, Centre for Addiction and Mental Health, Toronto, Ontario, Canada"
      ],
      "name": "Peter Selby"
    },
    {
      "affiliations": [
        "Department of Medicine (Division of Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Melissa Andrew"
    },
    {
      "affiliations": [
        "Primary Healthcare Research Unit, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada"
      ],
      "name": "Kris Aubrey-Bassler"
    },
    {
      "affiliations": [
        "Department of Family Medicine, Queen’s University, Kingston, Ontario, Canada"
      ],
      "name": "David Barber"
    },
    {
      "affiliations": [
        "Medicine Nephrology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada"
      ],
      "name": "Brendan Barrett"
    },
    {
      "affiliations": [
        "Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK"
      ],
      "name": "Christopher C Butler"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Noah Crampton"
    },
    {
      "affiliations": [
        "Elisabeth Bruyere Research Institute, University of Ottawa, Ottawa, Ontario, Canada"
      ],
      "name": "Simone Dahrouge"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Ali Damji"
    },
    {
      "affiliations": [
        "Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Robert Fowler"
    },
    {
      "affiliations": [
        "Department of Family Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Stephanie Garies"
    },
    {
      "affiliations": [
        "Université de Sherbrooke, Sherbrooke, Quebec, Canada"
      ],
      "name": "Catherine Hudon"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Jennifer Hulme"
    },
    {
      "affiliations": [
        "College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada",
        "Canadian Center for Vaccinology, Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Jennifer Isenor"
    },
    {
      "affiliations": [
        "Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada",
        "Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, Ontario, Canada"
      ],
      "name": "David J A Jenkins"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Rosemarie Lall"
    },
    {
      "affiliations": [
        "VITAM Research Center on Sustainable Health, Sherbrooke, Quebec, Canada"
      ],
      "name": "Annie LeBlanc"
    },
    {
      "affiliations": [
        "College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Christine Leong"
    },
    {
      "affiliations": [
        "Primary Care Research Centre, School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK"
      ],
      "name": "Paul Little"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, Women’s College Hospital, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, Women’s College Hospital, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada",
        "Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada"
      ],
      "name": "Aisha Lofters"
    },
    {
      "affiliations": [
        "Departments of Surgery and Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Sarvesh Logsetty"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada",
        "Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Sylvain Lother"
    },
    {
      "affiliations": [
        "CHUM Research Center, Université de Montréal’s affiliated hospital research center, Montréal, Québec, Canada",
        "Département de médecine de famille et de médecine d’urgence, Université de Montréal, Montréal, Québec, Canada"
      ],
      "name": "Marie-Thérèse Lussier"
    },
    {
      "affiliations": [
        "Department of Family Medicine, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada"
      ],
      "name": "Laura Maclaren"
    },
    {
      "affiliations": [
        "Public Health and General Practice, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand"
      ],
      "name": "Dee Mangin"
    },
    {
      "affiliations": [
        "Family Medicine, Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Emily Gard Marshall"
    },
    {
      "affiliations": [
        "Department of Surgery, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "John C Marshall"
    },
    {
      "affiliations": [
        "Family Medicine, Providence Health Care, Vancouver, British Columbia, Canada",
        "Family Practice, University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada"
      ],
      "name": "Rita McCracken"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Rahim Moineddin"
    },
    {
      "affiliations": [
        "Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Brianna Orava"
    },
    {
      "affiliations": [
        "VITAM – Research Centre on Sustainable Health, Sherbrooke, Québec, Canada",
        "Département de médecine de famille et de médecine d’urgence, Université Laval, Quebec City, Québec, Canada",
        "Laboratoire ARIMED, Saint-Charles-Borromée, Québec, Canada"
      ],
      "name": "Jean-Sébastien Paquette"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact (HEI), Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Jay Jae Hee Park"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada",
        "MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Nav Persaud"
    },
    {
      "affiliations": [
        "Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada",
        "Program for Health System and Technology Evaluation, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada"
      ],
      "name": "Valeria E Rac"
    },
    {
      "affiliations": [
        "Department of Family Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"
      ],
      "name": "Vivian R Ramsden"
    },
    {
      "affiliations": [
        "Alliance for Healthier Communities, Toronto, Ontario, Canada"
      ],
      "name": "Jennifer Rayner"
    },
    {
      "affiliations": [
        "College of Rehabilitation Sciences, Department of Respiratory Therapy, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Diana C. Sanchez-Ramirez"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Infectious Diseases, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Alberta, Canada"
      ],
      "name": "Lynora Saxinger"
    },
    {
      "affiliations": [
        "Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada"
      ],
      "name": "Haolun Shi"
    },
    {
      "affiliations": [
        "Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Manitoba Primary Care Research Network, Winnipeg, Manitoba, Canada"
      ],
      "name": "Alexander Singer"
    },
    {
      "affiliations": [
        "Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Manitoba Centre for Health Policy, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Rae Spiwak"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Anita Srivastava"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Research Institute, Humber River Health, Toronto, Ontario, Canada"
      ],
      "name": "Abhimanyu Sud"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact (HEI), Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Jean-Eric Tarride"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "South East Toronto Family Health Team, Toronto, Ontario, Canada"
      ],
      "name": "Deanna Telner"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada",
        "Joint Centre for Bioethics, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Ross E G Upshur"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Sakina Walji"
    },
    {
      "affiliations": [
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Evaluative Clinical Sciences Platform, Integrated Community Program, Sunnybrook Research Institute, Toronto, Ontario, Canada",
        "Sunnybrook Academic Family Health Team, Toronto, Ontario, Canada"
      ],
      "name": "Rachel Walsh"
    },
    {
      "affiliations": [
        "Departments of Medicine and of Family Medicine, McGill University, Montreal, Quebec, Canada",
        "Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada"
      ],
      "name": "Machelle Wilchesky"
    },
    {
      "affiliations": [
        "Centre for Health Services and Policy Research, University of British Columbia, Vancouver, British Columbia, Canada"
      ],
      "name": "Sabrina T Wong"
    },
    {
      "affiliations": [
        "Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada",
        "Dr. Gilles Arcand Centre for Health Equity, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada"
      ],
      "name": "Brianne Wood"
    },
    {
      "affiliations": [
        "Sections of Critical Care and Hematology/Medical Oncology, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Ryan Zarychanski"
    },
    {
      "affiliations": [
        "Dr. Gilles Arcand Centre for Health Equity, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada"
      ],
      "name": "Barb Zelek"
    },
    {
      "affiliations": [
        "Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Yoav Keynan"
    },
    {
      "affiliations": [
        "Faculty of Pharmacy, The University of British Columbia, Vancouver, British Columbia, Canada"
      ],
      "name": "Jolanta Piszczek"
    },
    {
      "affiliations": [
        "School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada",
        "Ontario Ministry of Health, Toronto, Ontario, Canada"
      ],
      "name": "Daniel Warshafsky"
    },
    {
      "affiliations": [
        "Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada",
        "Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada",
        "Department of Family and Community Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Andrew David Pinto"
    }
  ],
  "title": "Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID): protocol for a randomised controlled adaptive platform trial of treatments for acute SARS-CoV-2 infection in community settings",
  "uid": "23c13935-7ff3-57d7-adf4-85cfe5f66337"
}