Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial
Keywords
Abstract
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.
Dates
| Last Verified: | 05/31/2020 |
| First Submitted: | 03/24/2020 |
| Estimated Enrollment Submitted: | 03/24/2020 |
| First Posted: | 03/26/2020 |
| Last Update Submitted: | 06/24/2020 |
| Last Update Posted: | 06/28/2020 |
| Actual Study Start Date: | 04/20/2020 |
| Estimated Primary Completion Date: | 12/30/2020 |
| Estimated Study Completion Date: | 06/29/2021 |
Condition or disease
Intervention/treatment
Drug: Colchicine
Drug: Interferon Beta
Drug: Aspirin (ASA)
Drug: Rivaroxaban
Phase
Arm Groups
| 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 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 (ASA) 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. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | 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. |
Outcome
Primary Outcome Measures
1. Outpatient trial - Colchicine vs. control and Aspirin vs. control [45 days post randomization]
2. Inpatient trial - Interferon-β vs. control and Colchicine vs. control [45 days post randomization]
3. Inpatient trial - Aspirin and rivaroxaban vs. control [45 days post randomization]
Secondary Outcome Measures
1. Outpatient and Inpatient trials - Colchicine vs. control, Interferon-β vs. control [45 days post randomization]
2. Outpatient and Inpatient trials - Aspirin vs. control, Aspirin and rivaroxaban vs. control [45 days post randomization]
