Clinical trial NCT05614349: Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings
Official title: Canadian Adaptive Platform Trial of Treatments for COVID-19 in Community Settings
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Health Canada
name: Canadian Institutes of Health Research (CIHR)
First posted: 2022-11-14
Enrollment: 797
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: All-cause hospitalization or death rate
timeFrame: Day 28
Secondary outcomes:
measure: Time to recovery
timeFrame: Days 0-14
measure: Symptom severity
timeFrame: Days 0-28
measure: Rate of Post-acute sequelae of SARS-CoV-2
timeFrame: 90 days and 36 weeks
measure: Quality of life measurement (EQ-5D-5L)
timeFrame: Baseline, 21 days, 28 days, 90 days, and 36 weeks
measure: Early discontinuation and severe adverse events
timeFrame: Days 0-28
measure: Treatment costs
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: The Governors of the University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: The University of Manitoba
state: Manitoba
city: St. John's
country: Canada
facility: Eastern Health Newfoundland and Labrador
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Unity Health Toronto
state: Ontario
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
References: