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

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)

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

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.

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to participate in this study:

1. ≥ 18 years of age
2. 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.
3. Hospitalized at a participating centre
4. Primary reason for hospitalization or subsequent in-hospital illness is because of acute COVID19 infection
5. 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

1. On 10 days of steroid course and
2. 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:

1. Anticipated transfer to another hospital, within 72 hours, which is not a study site
2. Expected to not survive beyond 24 hours
3. 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:

1. Pregnant or breastfeeding;
2. Known hypersensitivity to imatinib;
3. Liver transaminases (either ALT or AST) > 5x upper limit of normal

Infliximab:

1. Known moderate or severe heart failure, per treating clinician, defined as New York Heart Association (NYHA) class III or IV
2. Known or suspected active tuberculosis
3. Known hypersensitivity to infliximab

Randomization LSALT:

1. Known hypersensitivity or prior use of LSALT peptide.
2. Pregnant or breastfeeding

Randomization Dex:

1. Receiving glucocorticoids for a specific, non-COVID-19 indication