Introduction: While effective vaccines and natural immunity have significantly reduced hospitalizations and the need for critical care, SARS-CoV-2 is now endemic and is expected to continue to pose a threat to health. New variants are expected to continue to emerge, and vaccines may become less effective. Effective and affordable therapeutics for SARS-CoV-2 that can be easily used in community settings are needed to accelerate recovery, reduce hospitalizations and mortality, and mitigate the development of post-acute sequelae of SARS-CoV-2, also known as "long COVID." In this paper we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). Methods and analysis: CanTreatCOVID is an open-label, individually randomized, multi-centre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalized 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 multi-faceted public communication strategy and outreach through primary care, out-patient clinics, and emergency departments. Participants are randomized 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 twice daily 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 hospitalization or death within 28 days of randomization. Ethics and dissemination: The CanTreatCOVID master protocol and sub-protocols 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 policymakers, presented at conferences, and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities.
