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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Artesunate; Drug: Imatinib; Drug: Infliximab; Drug: Dexamethasone; Drug: LSALT Peptide

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.

• Study Type: Interventional
• Enrollment (Estimated): 2900
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rob Fowler, MD; Phone Number: 416-480-6100; Email: rob.fowler@sunnybrook.ca
• Study Contact Backup: Name: Gail Klein; Phone Number: 416-480-5632; Email: CATCO@sunnybrook.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Calgary, Alberta, Canada, T1Y 6J4
      • Peter Lougheed Centre
    • Calgary, Alberta, Canada, T2V 1P9
      • Rockyview General Hospital
    • Calgary, Alberta, Canada, T3M 1M4
      • South Health Campus
    • Edmonton, Alberta, Canada, T6L 5X8
      • Grey Nuns Community Hospital
    • Edmonton, Alberta, Canada, T5R 4H5
      • Misericordia Community Hospital
    • Edmonton, Alberta, Canada, T5K0L4
      • Royal Alexandra Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hopsital
  • British Columbia
    • Kamloops, British Columbia, Canada, V2C2T1
      • Interior Health Royal Inland Hospital
    • North Vancouver, British Columbia, Canada, V7L 2L7
      • Lions Gate Hospital
    • Richmond, British Columbia, Canada, V6X 1A2
      • Richmond Hospital
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Vancouver General Hospital, Vancouver Coastal Health, Univeristy of British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Island Health - Royal Jubilee Hospital
    • Victoria, British Columbia, Canada, V8Z 6R5
      • Island Health - Victoria General Hospital
    • Victoria, British Columbia, Canada, V9S 2B7
      • Island Health - Nanaimo Regional General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface Hospital
    • Winnipeg, Manitoba, Canada, R3J 3M7
      • Grace General Hospital
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Regional Health Authority
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 0H6
      • Nova Scotia Health Authority
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System - Brampton Civic Hospital
    • Etobicoke, Ontario, Canada, M9V 1R8
      • William Osler Health System - Etobicoke General Hospital
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • London, Ontario, Canada, N6A 5A5
      • University Hospital
    • London, Ontario, Canada, N6A 5W9
      • Victoria Hospital
    • London, Ontario, Canada, N6A 4V2
      • St.Joseph'S Health Care
    • Markham, Ontario, Canada, L3P 7P3
      • Markham Stouffville Hospital
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Partners -Mississauga Site
    • Mississauga, Ontario, Canada, L5M 2N1
      • Trillium Health Partners-Credit Valley Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital - Civic Campus
    • Ottawa, Ontario, Canada, K1K 0T2
      • Hopital Montfort
    • Ottawa, Ontario, Canada, K2H 8P4
      • Queensway Carleton Hospital
    • Saint Catharines, Ontario, Canada, L2S 0A9
      • Niagara Health
    • Scarborough, Ontario, Canada, M1E4B9
      • Scarborough Health Network - Centenary Hospital
    • Scarborough, Ontario, Canada, M1P2V5
      • Scarborough Health Network - General Hospital
    • Scarborough, Ontario, Canada, M1W3W3
      • Scarborough Health Network - Birchmount Hospital
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4N3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada, M3M 0B2
      • Humber River Hospital
    • Toronto, Ontario, Canada, M5T2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M2K 1E1
      • North York General Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Michael Garron Hospital
    • Toronto, Ontario, Canada, M6R1B5
      • Unity Health Toronto - St. Joseph's Health Centre
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre-Glen Site Royal Victoria Hospital
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Québec - Université Laval
    • Québec, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec- Universite Laval
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Integre Universitaire de Sante et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Artesunate; Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care	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
Experimental: Imatinib; Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care	Drug: Imatinib; 400 mg enterally daily for 14 days plus standard of care
Experimental: Infliximab; Subjects will be randomized Artesunate vs Imatinib vs Infliximab vs standard of care	Drug: Infliximab; 5 mg/kg IV given one time, over 2 hours plus standard of care
Experimental: Dexamethasone; Subjects will be randomized between Dexamethasone vs 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
Experimental: LSALT Peptide; Subjects will be randomized between LSALT vs standard of care.	Drug: LSALT Peptide; 5 mg , 2 hour IV infusion once daily for up to 14 consecutive days
No Intervention: Control (Standard Care); 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?

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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: University of British Columbia; AbbVie; World Health Organization; Apotex Inc.; Arch Biopartners Inc.
• Investigators: Principal Investigator: Srinivas Murthy, MD, Provincial Health Services Authority

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial
• Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results
• Remdesivir in Patients With Severe Kidney Dysfunction. A Secondary Analysis of the CATCO Randomized Trial

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2020
• Primary Completion (Estimated): March 10, 2024
• Study Completion (Estimated): May 18, 2024

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Dexamethasone; Imatinib; Infliximab; Artesunate; LSALT Peptide
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Protein Kinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Tumor Necrosis Factor Inhibitors; Schistosomicides; Antiplatyhelmintic Agents; Dexamethasone; Imatinib Mesylate; Infliximab; Artesunate
• Other Study ID Numbers: 2114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

As per World Health Organization policies on data sharing in a Public Health Emergency, any clinical trial outcome data will be shared at the earliest possible opportunity. In addition, given the nature of this protocol, being performed across regions, the DSMB may access other regions trials, and possibly recommend alterations in study design based on accumulating data, through a centralized data repository being built under the auspices of the World Health Organization.

Data Sharing for Secondary Research Data from this study may be used for secondary research. All of the individual subject data collected during the trial will be made available after de-identification through expert determination. The SAP and Analytic Code will also be made available. This data will be available immediately following publication, with no end date, as part of data sharing requirements from journals and funding agencies.

• IPD Sharing Time Frame: Unknown and variable
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No