Treatments for COVID-19: Canadian Arm of the SOLIDARITY Trial

Study Overview
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Brief Summary
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This study is an adaptive, randomized, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization.

Detailed Description
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Subjects will be randomized, across one, two, three or up to four separate randomizations, to receive either standard-of-care products or the study medication plus standard of care, while being hospitalized for COVID-19. Randomization WHO: Imatinib vs Infliximab vs Artesunate vs Standard of care Randomization Dex: Dexamethasone vs Standard of care Randomization LSALT: LSALT Peptide vs Standard of care Hospitalized subjects will require blood sampling for screening and on days 1 and 5.

Official Title
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A Multi-centre, Adaptive, Randomized, Open-label, Controlled Clinical Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Patients (CATCO: Canadian Treatments for COVID-19), in Conjunction With the Public Health Emergency SOLIDARITY Trial (World Health Organization)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Artesunate
* Drug: Imatinib
* Drug: Infliximab
* Drug: Dexamethasone
* Drug: LSALT Peptide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each participant must meet all of the following inclusion criteria to participate in this study: ≥ 18 years of age Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen, within 14 days prior to randomization. Hospitalized at a participating centre Primary reason for hospitalization or subsequent in-hospital illness is because of acute COVID19 infection First admission for acute COVID19 In addition, there will be the below intervention-specific inclusion: Randomization WHO will have no other specific inclusion criteria. Randomization LSALT will have no other specific inclusion criteria. Randomization Dex will have the following specific inclusion criteria On 10 days of steroid course and Receiving any supplemental oxygen for 10 days Exclusion Criteria: All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study: Anticipated transfer to another hospital, within 72 hours, which is not a study site Expected to not survive beyond 24 hours Receiving one of the study drugs at time of enrolment In addition, there will be the below intervention-specific exclusions: Randomization WHO: These will be drug-specific exclusions; patients will still be eligible for randomization in Randomization WHO to the other available study drugs (in randomization WHO or subsequent randomizations). Artesunate: 1. Known hypersensitivity to artesunate Imatinib: Pregnant or breastfeeding; Known hypersensitivity to imatinib; Liver transaminases (either ALT or AST) > 5x upper limit of normal Infliximab: Known moderate or severe heart failure, per treating clinician, defined as New York Heart Association (NYHA) class III or IV Known or suspected active tuberculosis Known hypersensitivity to infliximab Randomization LSALT: Known hypersensitivity or prior use of LSALT peptide. Pregnant or breastfeeding Randomization Dex: 1. Receiving glucocorticoids for a specific, non-COVID-19 indication

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: Artesunate<br>Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care | Drug: Artesunate<br>* 2.4 mg/kg at 0 hours, 12 hours, 24 hours, and then daily for a total of 7 days plus standard of care<br>|
| Experimental: Imatinib<br>Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care | Drug: Imatinib<br>* 400 mg enterally daily for 14 days plus standard of care<br>|
| Experimental: Infliximab<br>Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care | Drug: Infliximab<br>* 5 mg/kg IV given one time, over 2 hours plus standard of care<br>|
| Experimental: Dexamethasone<br>Subjects will be randomized between Dexamethasone vs standard of care. | Drug: Dexamethasone<br>* 6 mg IV/oral for a further five days, followed by a five day taper of 4 mg x 2 days and 2 mg x 3 days, for a total 20 day steroid course. If randomized to standard of care, discontinue the corticosteroid on day 10<br>|
| Experimental: LSALT Peptide<br>Subjects will be randomized between LSALT vs standard of care. | Drug: LSALT Peptide<br>* 5 mg , 2 hour IV infusion once daily for up to 14 consecutive days<br>|
| No Intervention: Control (Standard Care)<br>This arm will receive standard supportive care guidelines for COVID-19. It is expected to vary regionally and may change throughout the trial based on new and emerging data on best care guidelines for patients. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Randomization WHO- Mortality | All-cause mortality, assessed at hospital discharge. | 28 days | 
| Randomization Dex- Clinical Status | Position on the WHO Ordinal scale at 28 days post-randomization. Ordinal Scale Table: 0 Uninfected; 1-3 Ambulatory; 4-5 Hospitalized/ Mild disease; 6-9 Hospitalized/ Severe Disease; 10 Death | 28 days | 
| Randomization LSALT- Respiratory support | Number of days respiratory support free days | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the clinical effectiveness of study drugs | To be compared to the control arm on duration of hospitalization | 24 months | 
| Need for invasive mechanical ventilation |  | 24 months | 
| CU admission, hospital and ICU length of stay, days alive and free of vasopressors, ventilation, and renal replacement therapy (RRT |  | 24 months | 
| Mortality | Mortality after Randomization | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artesunate, Infliximab, Imatinib, Dexamethasone, SARS-CoV-2, LSALT Peptide