Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial (ACTCOVID19)

Anti-Coronavirus Therapies to Prevent Progression of COVID-19, a Randomized Trial

ACT is a randomized clinical trial to assess therapies to reduce the clinical progression of COVID-19.

Study Overview

• Status: Completed
• Conditions: Severe Acute Respiratory Syndrome; Coronavirus
• Intervention / Treatment: Drug: Colchicine; Drug: Interferon-Beta; Drug: Aspirin; Drug: Rivaroxaban

Detailed Description

The ACT COVID-19 program consists of two parallel trials testing the effects of interventions in complementary populations in outpatients and inpatients.

In the outpatient study, symptomatic patients in the community who are COVID-19 positive and at high risk of disease progression: colchicine compared with control (anti-inflammatory); and ASA compared with control (anti-thrombotic); using a 2 x 2 factorial design. The primary outcome for colchicine vs. control is the composite of hospitalization or death. The primary outcome for ASA vs. control is the composite of hospitalization, death, or major thrombosis [myocardial infarction(MI), stroke, acute limb ischemia(ALI), or pulmonary embolism (PE)].

For inpatients, in symptomatic patients who are COVID-19 positive and who are hospitalized: colchicine is compared with control (anti-inflammatory), and the combination of ASA and rivaroxaban is compared with control (anti-thrombotic); using a 2 x 2 factorial design. The primary outcome for colchicine vs. control is the composite of high flow oxygen, mechanical ventilation, or death. The primary outcome for the combination of ASA and rivaroxaban vs. control is the composite of high flow oxygen, mechanical ventilation, death, or major thrombosis (MI, stroke, ALI, or PI).

*The Inpatient study previously also included a comparison of Interferon-β with control in a 2x2x2 design. The Interferon-β arm was closed to recruitment in November 2020.

• Study Type: Interventional
• Enrollment (Actual): 6667
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Amazonas
    • Manaus, Amazonas, Brazil
      • Hospital Adventista de Manaus
  • BA
    • Salvador, BA, Brazil
      • Prodal Saude S/A
  • ES
    • Vitoria, ES, Brazil
      • Hospital das Clinicas de Vitoria (Hospital Universitario Cassiano Antonio Moraes)
  • MG
    • Uberaba, MG, Brazil
      • Ubermed Serviços em Saúde Eireli - Hospital São Domingos
    • Uberlândia, MG, Brazil
      • Hospital de Clínicas da Universidade Federal de Uberlândia
  • Mount
    • Cuiabá, Mount, Brazil
      • Hospital Universitário Júlio Müller
  • Rio Grande Do Sul
    • Bento Goncalves, Rio Grande Do Sul, Brazil
      • Instituto Tacchini de Pesquisa em Saude / Hospital Tacchini
  • SP
    • São Carlos, SP, Brazil
      • Hospital Universitario Prof. Dr. Horacio Carlos Panepucci da Universidade Federal de Sao Carlos (HU-UFSCar)
    • São Paulo, SP, Brazil
      • Hospital Alemao Oswaldo Cruz
  • Sao Paulo
    • Votuporanga, Sao Paulo, Brazil
      • Santa Casa de Votuporanga
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • CardiAI Inc.
  • Ontario
    • Hamilton, Ontario, Canada, L8L2X2
      • Hamilton Health Sciences
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada
      • Southlake Regional Health Centre
    • Oakville, Ontario, Canada
      • Halton Healthcare/Oakville Trafalgar Memorial Hospital
    • St. Catharines, Ontario, Canada
      • Niagara Health System-St. Catharine's
    • Toronto, Ontario, Canada
      • Toronto Western Hospital Family Health Team
    • Windsor, Ontario, Canada
      • Windsor Regional Hospital
    • Woodstock, Ontario, Canada
      • Woodstock hospital
  • Quebec
    • Montreal, Quebec, Canada
      • CIUSSS de L'est-de-l'ile de Montreal, Hopital Maisonneuve-Rosemont
    • Montréal, Quebec, Canada
      • Centre hospitalier de l'Universite de Montreal (CHUM)
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Biomelab SAS
    • Barranquilla, Atlantico, Colombia
      • Clinica de la Costa Ltda
  • Santander
    • Bucaramanga, Santander, Colombia
      • Instituto de Neumologico del Oriente
• Ecuador
  • Guayas
    • Guayaquil, Guayas, Ecuador
      • Unicormed
  • Pichincha
    • Quito, Pichincha, Ecuador
      • Hospital de Especialidades Eugenio Espejo
    • Quito, Pichincha, Ecuador
      • Hospital Enrique Garces
    • Quito, Pichincha, Ecuador
      • Hospital General Pablo Arturo Suarez
  • Tungurahua
    • Ambato, Tungurahua, Ecuador
      • Oncoambato
• Egypt
  • Cairo, Egypt
    • National Hepatology and Tropical Medicine Research Institute
  • Cairo, Egypt
    • Abbasia Chest Hospital
  • Cairo, Egypt
    • Abbasia Fever Hospital
  • Fayoum, Egypt
    • Fayoum University hospital
  • Cairo
    • Giza, Cairo, Egypt
      • Giza Chest Hospital
• India
  • Karnataka
    • Bangalore, Karnataka, India
      • St. John's Medical college and Hospital
  • Maharashtra
    • Pune, Maharashtra, India
      • Bharathi Hospital and Research Center
    • Pune, Maharashtra, India
      • Sanjeevan Hospital
  • Punjab
    • Doraha, Punjab, India
      • Sidhu Hospital Pvt.Ltd
  • Tamil Nadu
    • Chengalpattu, Tamil Nadu, India
      • SRM Medical College Hospital & Research Center
  • Telangana
    • Hyderabad, Telangana, India
      • Aig Hospital
    • Secunderabad, Telangana, India
      • KIMS
• Nepal
  • Bagmati
    • Bharatpur-10, Bagmati, Nepal
      • Chitwan Medical College
    • Kathmandu, Bagmati, Nepal
      • Sahid Gangalal National Heart Center
  • Karnali
    • Surkhet, Karnali, Nepal
      • Province Hospital, Karnali Province
  • Province No. 1
    • Bhadrapur, Province No. 1, Nepal
      • Mechi Zonal Hospital
    • Biratnagar, Province No. 1, Nepal
      • Koshi Zonal Hospital
  • Province No.1
    • Kathmandu, Province No.1, Nepal
      • B.P. Koirala Institute of Health Sciences
• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan
      • Aga Khan University Hospital
    • Karachi, Sindh, Pakistan
      • Jinnah Postgraduate Medical Center
    • Karachi, Sindh, Pakistan
      • Tabba Heart Institute
• Philippines
  • Metro Manila
    • Manila, Metro Manila, Philippines
      • Philippine General Hospital
• Russian Federation
  • Barnaul, Russian Federation
    • Altai Regional Center for Medical Prevention
  • Moscow, Russian Federation
    • City Clinical Hospital No. 15 named after O.M. Filatova
  • Moscow, Russian Federation
    • National Medical Research Center for therapy and preventive medicine
  • Nizhny Novgorod, Russian Federation
    • City Clinical Hospital No. 3
  • Rostov-on-Don, Russian Federation
    • Rostov State Medical University
  • Sverdlovsk Region
    • Ekaterinburg, Sverdlovsk Region, Russian Federation
      • State Budgetary Health Care Institution of Sverdlovsk region "Central city clinical hospital # 6 Ekaterinburg"
    • Yekaterinburg, Sverdlovsk Region, Russian Federation
      • Central City Clinical Hospital No. 24
  • Tver Oblast
    • Tver, Tver Oblast, Russian Federation
      • Tver State Medical University
  • Voronezh Region
    • Voronezh, Voronezh Region, Russian Federation
      • Voronezh State Medical University named after N.N. Burdenko
• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Tiervlei Trial Centre
    • Cape Town, Western Cape, South Africa
      • University of Cape Town- Groote Schuur Hospital
    • George, Western Cape, South Africa
      • TASK Eden
• United Arab Emirates
  • Dubai, United Arab Emirates
    • Rashid Hospital, Dubai Health Authority
  • Dubai, United Arab Emirates
    • Thumbay Hospital Dubai
  • Dubai
    • Hatta, Dubai, United Arab Emirates
      • Hatta Hospital

Participation Criteria

Eligibility Criteria

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

Description

Outpatient trial:

Inclusion criteria:

1. Symptomatic and laboratory-confirmed diagnosis of COVID-19.
2. Age ≥ 30 years.
3. High risk: either age ≥70 or one of the following: male; obesity (BMI ≥30); chronic cardiovascular, respiratory or renal disease; active cancer; diabetes.
4. Within 7 days (ideally 72 hours) of diagnosis, or worsening clinically.

Exclusion criteria:

1. General: advanced kidney disease; advanced liver disease; pregnancy (known or potential) or lactation.
2. Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitor, azole antifungal, or macrolide antibiotic (except azithromycin).
3. ASA: allergy; high risk of bleeding, current or planned use of other anti-thrombotic drugs (e.g., P2Y12 inhibitors, direct oral anticoagulants, vitamin K antagonists, heparins)

Inpatient trial:

Inclusion criteria:

1. Symptomatic and laboratory-confirmed diagnosis of COVID-19.
2. Age ≥18 years.
3. Within 72 hours (ideally 24 hours) of admission, or worsening clinically.

Exclusion criteria:

1. General: advanced kidney disease; advanced liver disease, pregnancy (known or potential) or lactation, already ventilated for >72 hours.
2. Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin).
3. ASA and rivaroxaban: allergy; high risk of bleeding; estimated GFR <15 ml/min; current or planned use of P2Y12 inhibitors or therapeutic doses of anticoagulants* (e.g., direct oral anticoagulants, vitamin K antagonists, heparin, LMWH), current or planned use of strong inhibitors of both CYP 3A4 and P-gp (e.g., lopinavir/ritonavir, carbamazepine, ketoconazole). *Note that prophylactic doses of anticoagulants can be used in patients who are randomized to control.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; Outpatients: 0.6 mg twice daily for 3 days, then 0.6 mg once daily for 25 days (total 28 days). Inpatients: 1.2 mg followed by 0.6 mg 2 hours later, then 0.6 mg twice daily for 28 days. (*Depending on availability, 0.6 mg tablets can be substituted by 0.5 mg tablets for a regimen in outpatients of 0.5 mg twice daily for 3 days, then 0.5 mg once daily for 25 days [total 28 days]; and in inpatients of 1.0 mg followed by 0.5 mg 2 hours later, then 0.5 mg twice daily for 28 days).	Drug: Colchicine; oral medication
Experimental: Interferon Beta [This arm is now closed to recruitment]; Inpatients Only: 0.25 mg by subcutaneous injection on days 1, 3, 5 & 7	Drug: Interferon-Beta; subcutaneous injection
Experimental: Aspirin (ASA); Outpatients: 75 to 100 mg once daily for 28 days. Inpatients: 75 to 100 mg once daily for 28 days	Drug: Aspirin; oral medication
Experimental: Rivaroxaban; Inpatients Only: 2.5 mg twice daily for 28 days.	Drug: Rivaroxaban; oral medication
No Intervention: Usual Care (Control); Outpatients and Inpatients: No constraints for treating physicians on the therapies within the standard of care arm. All key co-interventions will be documented.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Outpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of hospitalization or death	45 days post randomization
Outpatient trial - Aspirin vs. control: Time from randomization to first occurrence of the composite of hospitalization, death or major thrombosis (MI, stroke, ALI, or PE)	45 days post randomization
Inpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or death	45 days post randomization
Inpatient trial - Aspirin and Rivaroxaban vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, death or major thrombosis (MI, stroke, ALI, or PE)	45 days post randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
Outpatient trial - Aspirin vs. control: Time from randomization to first occurrence of any thrombosis (MI, stroke, ALI, PE, or DVT)	45 days post randomization
Inpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or respiratory death	45 days post randomization
Inpatient trial - Aspirin vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or respiratory death	45 days post randomization
Inpatient trial - Aspirin vs. control: Time from randomization to first occurrence of any thrombosis (MI, stroke, ALI, PE, or DVT)	45 days post randomization

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Bayer
• Investigators: Principal Investigator: Richard Whitlock, MD PhD, Population Health Research Institute; Principal Investigator: Emilie Belley-Cote, MD PhD, Population Health Research Institute; Principal Investigator: John Eikelboom, MBBS MSc, Population Health Research Institute

Publications and helpful links

General Publications

• Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.
• Eikelboom JW, Jolly SS, Belley-Cote EP, Whitlock RP, Rangarajan S, Xu L, Heenan L, Bangdiwala SI, Luz Diaz M, Diaz R, Yusufali A, Kumar Sharma S, Tarhuni WM, Hassany M, Avezum A, Harper W, Wasserman S, Almas A, Drapkina O, Felix C, Lopes RD, Berwanger O, Lopez-Jaramillo P, Anand SS, Bosch J, Choudhri S, Farkouh ME, Loeb M, Yusuf S. Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022 Dec;10(12):1169-1177. doi: 10.1016/S2213-2600(22)00298-3. Epub 2022 Oct 10.
• Eikelboom JW, Jolly SS, Belley-Cote EP, Whitlock RP, Rangarajan S, Xu L, Heenan L, Bangdiwala SI, Tarhuni WM, Hassany M, Kontsevaya A, Harper W, Sharma SK, Lopez-Jaramillo P, Dans AL, Palileo-Villanueva LM, Avezum A, Pais P, Xavier D, Felix C, Yusufali A, Lopes RD, Berwanger O, Ali Z, Wasserman S, Anand SS, Bosch J, Choudhri S, Farkouh ME, Loeb M, Yusuf S. Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022 Dec;10(12):1160-1168. doi: 10.1016/S2213-2600(22)00299-5. Epub 2022 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2020
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: March 25, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: interferon; COVID-19; anti-inflammatory; coronavirus; aspirin; rivaroxaban; colchicine; antithrombotic; anti-viral
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Gout Suppressants; Aspirin; Interferons; Rivaroxaban; Colchicine; Interferon-beta
• Other Study ID Numbers: PHRI.ACT.COVID19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No