Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial
Anti-Coronavirus Therapies to Prevent Progression of Coronavirus Disease 2019 (COVID-19) Trial
ACT is a randomized clinical trial to assess therapies to reduce the clinical progression of
 COVID-19.
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.
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.