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

NCT04324463 | Completed Phase 3 DMC

• 1 other identifier: PHRI.ACT.COVID19
• Study Type: interventional
• Target: 6,667
• Locations: 12 countries
• Sites: 66

Brief Summary

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

Conditions

Coronavirus; Severe Acute Respiratory Syndrome

Keywords

COVID-19; coronavirus; interferon; colchicine; aspirin; rivaroxaban; anti-inflammatory; antithrombotic; anti-viral

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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

Study Arms (5)

Colchicine

EXPERIMENTAL

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

Interferon Beta [This arm is now closed to recruitment]

EXPERIMENTAL

Inpatients Only: 0.25 mg by subcutaneous injection on days 1, 3, 5 \& 7

Drug: Interferon-Beta

Aspirin (ASA)

EXPERIMENTAL

Outpatients: 75 to 100 mg once daily for 28 days. Inpatients: 75 to 100 mg once daily for 28 days

Drug: Aspirin

Rivaroxaban

EXPERIMENTAL

Inpatients Only: 2.5 mg twice daily for 28 days.

Drug: Rivaroxaban

Usual Care (Control)

NO INTERVENTION

Outpatients and Inpatients: No constraints for treating physicians on the therapies within the standard of care arm. All key co-interventions will be documented.

Interventions

Colchicine DRUG

oral medication

Colchicine

Interferon-Beta DRUG

subcutaneous injection

Interferon Beta [This arm is now closed to recruitment]

Aspirin DRUG

oral medication

Aspirin (ASA)

Rivaroxaban DRUG

oral medication

Rivaroxaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• General: advanced kidney disease; advanced liver disease; pregnancy (known or potential) or lactation.
• Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitor, azole antifungal, or macrolide antibiotic (except azithromycin).
• 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:
• Symptomatic and laboratory-confirmed diagnosis of COVID-19.
• Age ≥18 years.
• Within 72 hours (ideally 24 hours) of admission, or worsening clinically.
• General: advanced kidney disease; advanced liver disease, pregnancy (known or potential) or lactation, already ventilated for \>72 hours.
• Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin).
• 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.

Sponsors & Collaborators

• Population Health Research Institute: lead
• Bayer: collaborator

Study Sites (66)

Hospital Adventista de Manaus

Manaus, Amazonas, Brazil

Location

Hospital das Clinicas de Vitoria (Hospital Universitario Cassiano Antonio Moraes)

Vitória, Espírito Santo, Brazil

Location

Prodal Saude S/A

Salvador, Estado de Bahia, Brazil

Location

Ubermed Serviços em Saúde Eireli - Hospital São Domingos

Uberaba, Minas Gerais, Brazil

Location

Hospital de Clínicas da Universidade Federal de Uberlândia

Uberlândia, Minas Gerais, Brazil

Location

Hospital Universitario Julio Muller

Cuiabá, Mount, Brazil

Location

Instituto Tacchini de Pesquisa em Saude / Hospital Tacchini

Bento Gonçalves, Rio Grande do Sul, Brazil

Location

Hospital Universitario Prof. Dr. Horacio Carlos Panepucci da Universidade Federal de Sao Carlos (HU-UFSCar)

São Carlos, São Paulo, Brazil

Location

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Location

Santa Casa de Votuporanga

Votuporanga, São Paulo, Brazil

Location

CardiAI Inc.

Calgary, Alberta, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L2X2, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, Canada

Location

Halton Healthcare/Oakville Trafalgar Memorial Hospital

Oakville, Ontario, Canada

Location

Niagara Health System-St. Catharine's

St. Catharines, Ontario, Canada

Location

Toronto Western Hospital Family Health Team

Toronto, Ontario, Canada

Location

Windsor Regional Hospital

Windsor, Ontario, Canada

Location

Woodstock Hospital

Woodstock, Ontario, Canada

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Location

CIUSSS de L'est-de-l'ile de Montreal, Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Biomelab SAS

Barranquilla, Atlántico, Colombia

Location

Clinica de la Costa LTDA

Barranquilla, Atlántico, Colombia

Location

Instituto de Neumologico del Oriente

Bucaramanga, Santander Department, Colombia

Location

Unicormed

Guayaquil, Guayas, Ecuador

Location

Hospital de Especialidades Eugenio Espejo

Quito, Pichincha, Ecuador

Location

Hospital Enrique Garces

Quito, Pichincha, Ecuador

Location

Hospital General Pablo Arturo Suarez

Quito, Pichincha, Ecuador

Location

Oncoambato

Ambato, Tungurahua Province, Ecuador

Location

Giza Chest Hospital

Giza, Cairo Governorate, Egypt

Location

Fayoum University Hospital

Al Fayyum, Egypt

Location

Abbasia Chest Hospital

Cairo, Egypt

Location

Abbasia Fever Hospital

Cairo, Egypt

Location

National Hepatology and Tropical Medicine Research Institute

Cairo, Egypt

Location

St. John's Medical College and Hospital

Bangalore, Karnataka, India

Location

Bharathi Hospital and Research Center

Pune, Maharashtra, India

Location

Sanjeevan Hospital

Pune, Maharashtra, India

Location

Sidhu Hospital Pvt.Ltd

Dorāha, Punjab, India

Location

SRM Medical College Hospital & Research Center

Chengalpattu, Tamil Nadu, India

Location

AIG Hospital

Hyderabad, Telangana, India

Location

KIMS

Secunderabad, Telangana, India

Location

Chitwan Medical College

Bharatpur-10, Bagmati, Nepal

Location

Sahid Gangalal National Heart Center

Kathmandu, Bagmati, Nepal

Location

Province Hospital, Karnali Province

Surkhet, Karnali, Nepal

Location

Mechi Zonal Hospital

Bhadrapur, Province No. 1, Nepal

Location

Koshi Zonal Hospital

Biratnagar, Province No. 1, Nepal

Location

B.P. Koirala Institute of Health Sciences

Kathmandu, Province No.1, Nepal

Location

Aga Khan University Hospital

Karachi, Sindh, Pakistan

Location

Jinnah Postgraduate Medical Center

Karachi, Sindh, Pakistan

Location

Tabba Heart Institute

Karachi, Sindh, Pakistan

Location

Philippine General Hospital

Manila, National Capital Region, Philippines

Location

Central City Clinical Hospital No. 24

Yekaterinburg, Sverdlovsk Oblast, Russia

Location

State Budgetary Health Care Institution of Sverdlovsk region "Central city clinical hospital # 6 Ekaterinburg"

Yekaterinburg, Sverdlovsk Oblast, Russia

Location

Tver State Medical University

Tver', Tver Oblast, Russia

Location

Voronezh State Medical University named after N.N. Burdenko

Voronezh, Voronezh Oblast, Russia

Location

Altai Regional Center for Medical Prevention

Barnaul, Russia

Location

City Clinical Hospital No. 15 named after O.M. Filatova

Moscow, Russia

Location

National Medical Research Center for Therapy and Preventive Medicine

Moscow, Russia

Location

City Clinical Hospital No. 3

Nizhny Novgorod, Russia

Location

Rostov State Medical University

Rostov-on-Don, Russia

Location

Tiervlei Trial Centre

Cape Town, Western Cape, South Africa

Location

University of Cape Town- Groote Schuur Hospital

Cape Town, Western Cape, South Africa

Location

TASK Eden

George, Western Cape, South Africa

Location

Hatta Hospital

Hatta, Dubai, United Arab Emirates

Location

Rashid Hospital, Dubai Health Authority

Dubai, United Arab Emirates

Location

Thumbay Hospital Dubai

Dubai, United Arab Emirates

Location

Related Publications (4)

• Fischer AL, Messer S, Riera R, Martimbianco ALC, Stegemann M, Estcourt LJ, Weibel S, Monsef I, Andreas M, Pacheco RL, Skoetz N. Antiplatelet agents for the treatment of adults with COVID-19. Cochrane Database Syst Rev. 2023 Jul 25;7(7):CD015078. doi: 10.1002/14651858.CD015078.

  PMID: 37489818 DERIVED

• 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.

  PMID: 36228641 DERIVED

• 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.

  PMID: 36228639 DERIVED

• 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.

  PMID: 34658014 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Severe Acute Respiratory Syndrome; COVID-19

Interventions

Colchicine; Interferon-beta; Aspirin; Rivaroxaban

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiophenes; Sulfur Compounds; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, parallel group, factorial, randomized controlled trial

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 27, 2020
• Study Start: April 21, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3); PH (1); EG (5); EC (5); RU (9); AE (3); NE (6); BR (10); CO (3); CA (11); IN (7); PA (3)