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

CanTreatCOVID is an open-label, individually randomized, multi-centre, national trial. CanTreatCOVID aims to establish an adaptive platform trial aimed at evaluating the clinical- and cost-effectiveness, practical challenges, and outcomes of therapeutics for SARS-CoV-2 for non-hospitalized patients in Canada. Participants will be randomized to receive usual care (i.e. supportive care and symptom relief) or a study therapeutic, which will be determined by the Canadian COVID-19 Out-Patient Therapeutics Committee. The primary outcomes being evaluated is hospitalization and/or death at 28 days, as well as time to recovery.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Paxlovid; Drug: Antioxidant

Detailed Description

While public health measures and vaccines have reduced the impact of SARS-CoV-2 on hospitalization and death, most scientists predict this virus will become endemic and new variants will continue to emerge. Effective and affordable therapeutics for SARS-CoV-2 that can be easily used in community settings are needed to accelerate recovery, prevent hospitalizations and deaths, and to minimize the development of post-acute sequelae of SARS-CoV-2 ("long COVID"). Most randomized controlled trials (RCT) of therapeutics to date have included participants who have not been vaccinated and who did not have previous infections. The Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID) will evaluate the clinical effectiveness and cost-effectiveness of therapeutics for SARS-CoV-2 in non-hospitalized patients. Adaptive platform trials (APTs) are designed to compare multiple therapies in an efficient manner and allow us to respond to the dynamic nature of the COVID-19 pandemic. Therapeutics to be evaluated will be identified through a transparent Canadian COVID-19 Out-Patient Therapeutics Committee. The co-primary outcomes are all-cause hospitalization and/or death at 28 days as well as time to recovery, and key secondary outcomes include, symptom severity, incidence of post-acute sequelae of SARS-CoV-2, quality of life, and cost-effectiveness of each therapeutic. 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 EDs.

• Study Type: Interventional
• Enrollment (Actual): 797
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • The Governors of the University of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z IY6
      • University of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, Manitoba
      • The University of Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Health Newfoundland and Labrador
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto
  • Quebec
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 50 years and older or 18-49 with 1 or more chronic high-risk medical conditions, and/or immunosuppression: chronic respiratory disease (including COPD, cystic fibrosis and asthma requiring at least daily use of preventative and/or reliever medication); chronic heart or vascular disease; chronic kidney disease; chronic liver disease; chronic neurological disease (including dementia, stroke, epilepsy); severe and profound learning disability; Down's syndrome; diabetes (Type 1 or Type 2); immunosuppression: primary (e.g. inherited immune disorders resulting from genetic mutations) or secondary due to disease or treatment (e.g. sickle cell, HIV, cancer, chemotherapy); solid organ, bone marrow and stem cell transplant recipients; morbid obesity (BMI >35); severe mental illness; care home resident.
• Confirmed SARS-CoV-2 by nucleic acid testing or rapid antigen testing with proof of a positive test provided via a picture of the result
• Able to be enrolled and begin the study therapeutic within 5 days of onset of symptoms associated with SARS-CoV-2 infection

Exclusion Criteria:

• Admitted to hospital or in an ED for more than 24 hours
• Previously randomized to CanTreatCOVID
• Currently participating in a clinical trial of a therapeutic agent for acute SARS-CoV-2 infection that is not/suspected not compatible with the study therapeutics
• Already taking a study therapeutic or contraindication to a study therapeutic
• Inability for participant or caregiver to provide informed consent

Paxlovid Exclusion Criteria include:

• History of clinically significant hypersensitivity to the active substances in Paxlovid™ (nirmatrelvir /ritonavir) or to any of its excipients.
• Patients with known rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
• Patients with known current severe liver impairment (characterized by severe ascites, encephalopathy, jaundice, or prolonged INR. People with liver disease without any of these features are eligible).
• Is a recipient of a solid organ transplant and taking immunosuppressant medications.
• Patients with known moderate or severe renal disease (defined as CKD stage 3, 4 or 5 or current acute kidney injury or most recent eGFR in the past 6 months <60 ml/min).
• Currently taking Paxlovid™.
• Clinical requirement to continue taking a drug which is contraindicated or not recommended for administration with Paxlovid™ in the context of CanTreatCOVID or is taking a drug which in the opinion of the investigator would put the subject at unacceptable risk.
• Has a known or suspected pregnancy.
• Is breastfeeding.
• Is of childbearing potential and is not willing to use a highly effective contraceptive

Antioxidant Exclusion Criteria include:

• Has a known or suspected pregnancy.
• Is breastfeeding.
• Is of childbearing potential and is not willing to use a highly effective contraceptive.
• Has allergy or intolerance to selenium, zinc, lycopene, vitamin C, ascorbyl palmitate, hypromellose, microcrystalline cellulose, or sodium stearyl fumarate
• Is taking warfarin as a preventive measure.
• Has advanced chronic kidney disease (CKD stage 3: eGFR ≥30 to <60 mL/min, and severe renal impairment (eGFR <30 ml/min, CKD stage 4-5)
• Has liver disease awaiting transplantation.
• Has a history of calcium oxalate kidney stones.
• Has a diagnosis of head and neck cancer within the past 5 years
• Has medical history of non-melanoma skin cancer
• Is taking selenium (≥300ug/day), zinc (≥40mg/day), lycopene (≥45mg/day), and vitamin C (≥1500mg/day) supplements at baseline
• Is consuming omega-3 fatty acids at baseline and is unwilling to stop during the intervention period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Usual care (i.e., supportive care and symptom relief)
Experimental: Paxlovid; Nirmatrelvir/ritonavir (Paxlovid™) BD x 5 days (this arm has been closed of Sept 30th 2024)	Drug: Paxlovid; This adaptive platform trial will assess therapeutics for SARS-CoV-2 in out-patient settings. The first intervention arm is Paxlovid.
Experimental: Antioxidant Therapy - Intervention (arm 3); Antioxidant therapy (comprising of selenium, zinc, lycopene, and vitamin C)	Drug: Antioxidant; Antioxidant therapy (comprising of selenium, zinc, lycopene, and vitamin C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause hospitalization or death rate	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom severity	Symptoms severity will be assessed using the questions: "How well are you feeling today? Please rate how you are feeling now using a scale of 1 - 4, where 1 is no symptoms, and 4 is very severe symptoms" and by rating symptoms, if present, as "No problem, mild problem, moderate problem, or major problem."	Days 0-28
Early discontinuation and severe adverse events		Days 0-28
Treatment costs	Cost-utility analysis will be calculated as the incremental cost per QALY gained.	12 and 24 months
Rate of Post-acute sequelae of SARS-CoV-2		90 days and 36 weeks
Time to recovery	Defined as the first instance that a participant reports feeling fully recovered after enrolment	Days 0-14
Quality of life measurement (EQ-5D-5L)	Measured by EQ-5D-5L questionnaire on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine	Baseline, 21 days, 28 days, 90 days, and 36 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR); Health Canada

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Actual): April 28, 2025
• Study Completion (Estimated): June 28, 2025

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: November 9, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Protective Agents; Nirmatrelvir and ritonavir drug combination; Antioxidants
• Other Study ID Numbers: CTO 4133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Our team is dedicated to making data accessible to researchers upon request.
• IPD Sharing Time Frame: End of study (TBD) and upon request until 15yrs after study completion.
• IPD Sharing Access Criteria: Study PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No