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

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ClinicalTrials.gov Identifier: NCT04324463
Recruitment Status : Recruiting
First Posted : March 27, 2020
Last Update Posted : June 29, 2020
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Population Health Research Institute

Tracking Information
First Submitted Date  ICMJE March 25, 2020
First Posted Date  ICMJE March 27, 2020
Last Update Posted Date June 29, 2020
Actual Study Start Date  ICMJE April 21, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2020)
  • Outpatient trial - Colchicine vs. control and Aspirin vs. control [ Time Frame: 45 days post randomization ]
    composite of hospitalization or death
  • Inpatient trial - Interferon-β vs. control and Colchicine vs. control [ Time Frame: 45 days post randomization ]
    invasive mechanical ventilation or death
  • Inpatient trial - Aspirin and rivaroxaban vs. control [ Time Frame: 45 days post randomization ]
    invasive mechanical ventilation or death
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2020)
  • Outpatients: Hospital Admission or Death [ Time Frame: Up to 6 weeks post randomization ]
    In outpatients with COVID-19, the occurrence of hospital admission or death
  • Inpatients: Invasive mechanical ventilation or mortality [ Time Frame: Up to 6 weeks post randomization ]
    Patients intubated or requiring imminent intubation at the time of randomization will only be followed for the primary outcome of death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2020)
  • Outpatient and Inpatient trials - Colchicine vs. control, Interferon-β vs. control [ Time Frame: 45 days post randomization ]
    disease progression by 2 points on a 7-point scale
  • Outpatient and Inpatient trials - Aspirin vs. control, Aspirin and rivaroxaban vs. control [ Time Frame: 45 days post randomization ]
    composite of major adverse cardiovascular events (MI, stroke, ALI, VTE, death), and disease progression by 2 points on a 7-point scale
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial
Official Title  ICMJE Anti-Coronavirus Therapies to Prevent Progression of COVID-19, a Randomized Trial
Brief Summary ACT is a randomized clinical trial to assess therapies to reduce the clinical progression of COVID-19.
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; and the co-primary outcome is disease progression by 2 points on a 7-point scale. The primary outcome for ASA vs. control is the composite of hospitalization or death; and the co-primary outcomes are the composite of major adverse cardiovascular events (MI, stroke, ALI, VTE, death), and disease progression by 2 points on a 7-point scale.

For inpatients, in symptomatic patients who are COVID-19 positive and who are hospitalized: interferon-β is compared with control (anti-viral); 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 x 2 factorial design. The primary outcome for interferon-β vs. control, and for colchicine vs. control is the composite of invasive mechanical ventilation or death; and the co-primary outcome is disease progression by 2 points on a 7-point scale. The primary outcome for the combination of ASA and rivaroxaban vs. control is the composite of invasive mechanical ventilation or death; and the co-primary outcomes are the composite of major adverse cardiovascular events (MI, stroke, ALI, VTE, death) and disease progression by 2 points on a 7-point scale.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open-label, parallel group, factorial, randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus
  • Severe Acute Respiratory Syndrome
Intervention  ICMJE
  • Drug: Colchicine
    oral medication
  • Drug: Interferon-Beta
    subcutaneous injection
  • Drug: Aspirin
    oral medication
  • Drug: Rivaroxaban
    oral medication
Study Arms  ICMJE
  • 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).

    Intervention: Drug: Colchicine
  • Experimental: Interferon Beta

    Inpatients Only:

    0.25 mg by subcutaneous injection on days 1, 3, 5 & 7

    Intervention: Drug: Interferon-Beta
  • Experimental: Aspirin (ASA)

    Outpatients:

    75 to 100 mg once daily for 28 days.

    Inpatients:

    75 to 100 mg once daily for 28 days

    Intervention: Drug: Aspirin
  • Experimental: Rivaroxaban

    Inpatients Only:

    2.5 mg twice daily for 28 days.

    Intervention: Drug: Rivaroxaban
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 16, 2020)
4000
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2020)
1500
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Outpatient trial:

Inclusion criteria:

  1. Symptomatic and laboratory-confirmed diagnosis of COVID-19.
  2. Age ≥18 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. Interferon-ß: known monoclonal gammopathy, history of severe depression/anxiety.
  3. Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin).
  4. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ACT COVID-19 Study Coordinator 905-297-3479 ACT.ProjectTeam@PHRI.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04324463
Other Study ID Numbers  ICMJE PHRI.ACT.COVID19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Population Health Research Institute
Study Sponsor  ICMJE Population Health Research Institute
Collaborators  ICMJE Bayer
Investigators  ICMJE
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
PRS Account Population Health Research Institute
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP