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.
Drug: Artesunate
2.4 mg/kg at 0 hours, 12 hours, 24 hours, and then daily for a total of 7 days plus standard of care
Drug: Imatinib
400 mg enterally daily for 14 days plus standard of care
Drug: Infliximab
5 mg/kg IV given one time, over 2 hours plus standard of care
Drug: Dexamethasone
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
Drug: LSALT Peptide
5 mg , 2 hour IV infusion once daily for up to 14 consecutive days
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
Peter Lougheed Centre
Calgary, Alberta, Canada
Foothills Medical Centre
Calgary, Alberta, Canada
Rockyview General Hospital
Calgary, Alberta, Canada
South Health Campus
Calgary, Alberta, Canada
Royal Alexandra Hospital
Edmonton, Alberta, Canada
Misericordia Community Hospital
Edmonton, Alberta, Canada
University of Alberta Hopsital
Edmonton, Alberta, Canada
Grey Nuns Community Hospital
Edmonton, Alberta, Canada
Interior Health Royal Inland Hospital
Kamloops, British Columbia, Canada
Lions Gate Hospital
North Vancouver, British Columbia, Canada
Richmond Hospital
Richmond, British Columbia, Canada
Vancouver General Hospital, Vancouver Coastal Health, Univeristy of British Columbia
Vancouver, British Columbia, Canada
St Paul's Hospital
Vancouver, British Columbia, Canada
Island Health - Royal Jubilee Hospital
Victoria, British Columbia, Canada
Island Health - Victoria General Hospital
Victoria, British Columbia, Canada
Island Health - Nanaimo Regional General Hospital
Victoria, British Columbia, Canada
St. Boniface Hospital
Winnipeg, Manitoba, Canada
Health Sciences Centre
Winnipeg, Manitoba, Canada
Grace General Hospital
Winnipeg, Manitoba, Canada
Eastern Regional Health Authority
Saint John's, Newfoundland and Labrador, Canada
Nova Scotia Health Authority
Halifax, Nova Scotia, Canada
Royal Victoria Regional Health Centre
Barrie, Ontario, Canada
William Osler Health System - Brampton Civic Hospital
Brampton, Ontario, Canada
William Osler Health System - Etobicoke General Hospital
Etobicoke, Ontario, Canada
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada
St.Joseph's Health Care
London, Ontario, Canada
University Hospital
London, Ontario, Canada
Victoria Hospital
London, Ontario, Canada
Markham Stouffville Hospital
Markham, Ontario, Canada
Trillium Health Partners -Mississauga Site
Mississauga, Ontario, Canada
Trillium Health Partners-Credit Valley Hospital
Mississauga, Ontario, Canada
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada
Hôpital Montfort
Ottawa, Ontario, Canada
The Ottawa Hospital - Civic Campus
Ottawa, Ontario, Canada
Queensway Carleton Hospital
Ottawa, Ontario, Canada
Niagara Health
Saint Catharines, Ontario, Canada
Scarborough Health Network - Centenary Hospital
Scarborough, Ontario, Canada
Scarborough Health Network - General Hospital
Scarborough, Ontario, Canada
Scarborough Health Network - Birchmount Hospital
Scarborough, Ontario, Canada
Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, Canada
North York General Hospital
Toronto, Ontario, Canada
Humber River Hospital
Toronto, Ontario, Canada
Michael Garron Hospital
Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Toronto Western Hospital
Toronto, Ontario, Canada
Unity Health Toronto - St. Joseph's Health Centre
Toronto, Ontario, Canada
Centre Hospitalier de l'Université de Montréal (CHUM)
Montréal, Quebec, Canada
McGill University Health Centre-Glen Site Royal Victoria Hospital
Montréal, Quebec, Canada
CHU de Québec - Université Laval
Québec, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
Québec, Quebec, Canada
Centre Intégré Universitaire de Santé et de Services Sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, Canada
Srinivas Murthy, MD, Principal Investigator
Provincial Health Services Authority