ACT Study
Anti-Coronavirus Therapies to prevent COVID-19 progression trial. This study will evaluate anti-inflammatory and anti-thrombotic therapy to determine whether they prevent clinical progression of COVID-19 in outpatients and inpatients.
Outpatient
Randomization (factorial randomization)
- Anti-inflammatory: Colchicine vs. control (usual care)
- Antithrombotic: Acetylsalicylic acid (ASA) vs. control (usual care)
Inclusion
- Symptomatic and laboratory-confirmed diagnosis of COVID-19.
- Age ≥18 years.
- High risk: either age ≥70 or at least 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.
Exclusion
- General: advanced kidney disease (eGFR <15 mL/min/1.73m2)*; advanced liver disease; pregnancy (known or potential) or lactation
- Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitor, systemic azole antifungal, or macrolide antibiotic (except azithromycin).
- ASA: allergy or planned use; high risk of bleeding, current or planned use of other anti-thrombotic drugs (e.g., P2Y12 inhibitors, direct oral anticoagulants, vitamin K antagonists, heparins).
(*Patients >70 years, with known chronic kidney disease, or with a history of diabetes for more than 10 years must have creatinine [eGFR] result available from within 3 months prior to randomization)
Inpatient
RANDOMIZATION (factorial randomizations)
- Anti-inflammatory: colchicine vs. control (Usual care)
- Antithrombotic: combination of ASA and rivaroxaban vs. control (Usual care)
Inclusion
- Symptomatic and laboratory diagnosis of COVID-19
- Age ≥18 years of age.
- Within 72 hours (ideally 24 hours) of hospital admission, or worsening clinically.
Exclusion
- General: advanced kidney disease (eGFR <15 mL/min/1.73m2), 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 inhibitor, systemic azole antifungal, or macrolide antibiotic (except azithromycin).
- ASA and rivaroxaban: allergy or planned use of rivaroxaban; high risk of bleeding; 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 anticoagulant can
be used in patients who are not randomized to the
combination of ASA and rivaroxaban.
(*Patients must have creatinine [eGFR] result available from within 72 hours before randomization).