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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Paxlovid
* Drug: Other
* Other: Other


Participation Criteria
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Eligibility Criteria
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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: 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). 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paxlovid<br>Nirmatrelvir/ritonavir (Paxlovid™) BD x 5 days | Drug: Paxlovid<br>* This adaptive platform trial will assess therapeutics for SARS-CoV-2 in out-patient settings. The first intervention arm is Paxlovid.<br>|
| No Intervention: Control group<br>Usual care (i.e., supportive care and symptom relief) | |
| Experimental: Other Emerging Interventions (arm 3)<br>Additional treatment regimens will be decided by the Canadian COVID-19 Out-Patient Therapeutics Committee based on doses and durations studied in past trials and the latest evidence | Drug: Other<br>* As this trial progresses, therapeutics for SARS-CoV-2 in out-patient settings to be evaluated will be determined by the Canadian COVID-19 Out-Patient Therapeutics Committee, which will evaluate the latest evidence on new therapeutics and makes recommendations to the Steering Committee.<br>|
| Experimental: Other Emerging Interventions (arm 4)<br>Additional treatment regimens will be decided by the Canadian COVID-19 Out-Patient Therapeutics Committee based on doses and durations studied in past trials and the latest evidence | Other: Other<br>* As this trial progresses, therapeutics for SARS-CoV-2 in out-patient settings to be evaluated will be determined by the Canadian COVID-19 Out-Patient Therapeutics Committee, which will evaluate the latest evidence on new therapeutics and makes recommendations to the Steering Committee.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause hospitalization or death rate |  | Day 28 | 
| Time to recovery | Defined as the first instance that a participant reports feeling fully recovered after entolment | Days 0-14 | 

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 | 
| Rate of Post-acute sequelae of SARS-CoV-2 |  | 90 days and 36 weeks | 
| Quality of life | 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 | 
| 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 |