Clinical trial NCT04330690: Treatments for COVID-19: Canadian Arm of the SOLIDARITY Trial
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
Keywords: Artesunate
Infliximab
Imatinib
Dexamethasone
SARS-CoV-2
LSALT Peptide
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: AbbVie
name: Apotex Inc.
name: World Health Organization
name: University of British Columbia
name: Arch Biopartners Inc.
First posted: 2020-04-01
Enrollment: 2900
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: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Randomization WHO- Mortality
timeFrame: 28 days
measure: Randomization Dex- Clinical Status
timeFrame: 28 days
measure: Randomization LSALT- Respiratory support
timeFrame: 28 days
Secondary outcomes:
measure: Evaluation of the clinical effectiveness of study drugs
timeFrame: 24 months
measure: Need for invasive mechanical ventilation
timeFrame: 24 months
measure: CU admission, hospital and ICU length of stay, days alive and free of vasopressors, ventilation, and renal replacement therapy (RRT
timeFrame: 24 months
measure: Mortality
timeFrame: 12 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Calgary
country: Canada
facility: Rockyview General Hospital
state: Alberta
city: Calgary
country: Canada
facility: South Health Campus
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Misericordia Community Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hopsital
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Community Hospital
state: Alberta
city: Kamloops
country: Canada
facility: Interior Health Royal Inland Hospital
state: British Columbia
city: North Vancouver
country: Canada
facility: Lions Gate Hospital
state: British Columbia
city: Richmond
country: Canada
facility: Richmond Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital, Vancouver Coastal Health, Univeristy of British Columbia
state: British Columbia
city: Vancouver
country: Canada
facility: St Paul's Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Island Health - Royal Jubilee Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Island Health - Victoria General Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Island Health - Nanaimo Regional General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Winnipeg
country: Canada
facility: Grace General Hospital
state: Manitoba
city: Saint John's
country: Canada
facility: Eastern Regional Health Authority
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Brampton
country: Canada
facility: William Osler Health System - Brampton Civic Hospital
state: Ontario
city: Etobicoke
country: Canada
facility: William Osler Health System - Etobicoke General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: St.Joseph's Health Care
state: Ontario
city: London
country: Canada
facility: University Hospital
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Markham
country: Canada
facility: Markham Stouffville Hospital
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners -Mississauga Site
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners-Credit Valley Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Ottawa
country: Canada
facility: Hôpital Montfort
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Civic Campus
state: Ontario
city: Ottawa
country: Canada
facility: Queensway Carleton Hospital
state: Ontario
city: Saint Catharines
country: Canada
facility: Niagara Health
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Health Network - Centenary Hospital
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Health Network - General Hospital
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Health Network - Birchmount Hospital
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Humber River Hospital
state: Ontario
city: Toronto
country: Canada
facility: Michael Garron Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto - St. Joseph's Health Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre-Glen Site Royal Victoria Hospital
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec - Université Laval
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Intégré Universitaire de Santé et de Services Sociaux de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
Study officials:
affiliation: Provincial Health Services Authority
name: Srinivas Murthy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ali K, Azher T, Baqi M, Binnie A, Borgia S, Carrier FM, Cavayas YA, Chagnon N, Cheng MP, Conly J, Costiniuk C, Daley P, Daneman N, Douglas J, Downey C, Duan E, Duceppe E, Durand M, English S, Farjou G, Fera E, Fontela P, Fowler R, Fralick M, Geagea A, Grant J, Harrison LB, Havey T, Hoang H, Kelly LE, Keynan Y, Khwaja K, Klein G, Klein M, Kolan C, Kronfli N, Lamontagne F, Lau R, Fralick M, Lee TC, Lee N, Lim R, Longo S, Lostun A, MacIntyre E, Malhame I, Mangof K, McGuinty M, Mergler S, Munan MP, Murthy S, O'Neil C, Ovakim D, Papenburg J, Parhar K, Parvathy SN, Patel C, Perez-Patrigeon S, Pinto R, Rajakumaran S, Rishu A, Roba-Oshin M, Rushton M, Saleem M, Salvadori M, Scherr K, Schwartz K, Semret M, Silverman M, Singh A, Sligl W, Smith S, Somayaji R, Tan DHS, Tobin S, Todd M, Tran TV, Tremblay A, Tsang J, Turgeon A, Vakil E, Weatherald J, Yansouni C, Zarychanski R; Canadian Treatments for COVID-19 (CATCO); Association of Medical Microbiology and Infectious Disease Canada (AMMI) Clinical Research Network and the Canadian Critical Care Trials Group. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial. CMAJ. 2022 Feb 22;194(7):E242-E251. doi: 10.1503/cmaj.211698. Epub 2022 Jan 19.
citation: WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, Alejandria MM, Hernandez Garcia C, Kieny MP, Malekzadeh R, Murthy S, Reddy KS, Roses Periago M, Abi Hanna P, Ader F, Al-Bader AM, Alhasawi A, Allum E, Alotaibi A, Alvarez-Moreno CA, Appadoo S, Asiri A, Aukrust P, Barratt-Due A, Bellani S, Branca M, Cappel-Porter HBC, Cerrato N, Chow TS, Como N, Eustace J, Garcia PJ, Godbole S, Gotuzzo E, Griskevicius L, Hamra R, Hassan M, Hassany M, Hutton D, Irmansyah I, Jancoriene L, Kirwan J, Kumar S, Lennon P, Lopardo G, Lydon P, Magrini N, Maguire T, Manevska S, Manuel O, McGinty S, Medina MT, Mesa Rubio ML, Miranda-Montoya MC, Nel J, Nunes EP, Perola M, Portoles A, Rasmin MR, Raza A, Rees H, Reges PPS, Rogers CA, Salami K, Salvadori MI, Sinani N, Sterne JAC, Stevanovikj M, Tacconelli E, Tikkinen KAO, Trelle S, Zaid H, Rottingen JA, Swaminathan S. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2021 Feb 11;384(6):497-511. doi: 10.1056/NEJMoa2023184. Epub 2020 Dec 2.
citation: Cheng M, Fowler R, Murthy S, Pinto R, Sheehan NL, Tseng A. Remdesivir in Patients With Severe Kidney Dysfunction: A Secondary Analysis of the CATCO Randomized Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2229236. doi: 10.1001/jamanetworkopen.2022.29236.
citation: Lau VI, Fowler R, Pinto R, Tremblay A, Borgia S, Carrier FM, Cheng MP, Conly J, Costiniuk CT, Daley P, Duan E, Durand M, Fontela PS, Farjou G, Fralick M, Geagea A, Grant J, Keynan Y, Khwaja K, Lee N, Lee TC, Lim R, O'Neil CR, Papenburg J, Semret M, Silverman M, Sligl W, Somayaji R, Tan DHS, Tsang JLY, Weatherald J, Yansouni CP, Zarychanski R, Murthy S; E-CATCO authors, AMMI Clinical Research Network and Canadian Critical Care Trials Group. Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial. CMAJ Open. 2022 Sep 6;10(3):E807-E817. doi: 10.9778/cmajo.20220077. Print 2022 Jul-Sep.
citation: Essai CATCO (Canadian Treatments for COVID-19); pour le Reseau de recherche clinique de l'Association pour la microbiologie medicale et l'infectiologie Canada (AMMI Canada) le Groupe canadien de recherche en soins intensifs (CCCTG). Remdesivir chez les patients hospitalises pour la COVID-19 au Canada: essai clinique randomise et controle. CMAJ. 2022 May 24;194(20):E713-E723. doi: 10.1503/cmaj.211698-f. French.
citation: Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.