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

Population Health Research Institute (PHRI)

Status and phase: Completed; Phase 3

Conditions: Severe Acute Respiratory Syndrome; Coronavirus

Treatments: Drug: Rivaroxaban; Drug: Aspirin; Drug: Colchicine; Drug: Interferon-Beta

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04324463

PHRI.ACT.COVID19

Details and patient eligibility

About

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

Full 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. The primary outcome for ASA vs. control is the composite of hospitalization, death, or major thrombosis [myocardial infarction(MI), stroke, acute limb ischemia(ALI), or pulmonary embolism (PE)].

For inpatients, in symptomatic patients who are COVID-19 positive and who are hospitalized: 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 factorial design. The primary outcome for colchicine vs. control is the composite of high flow oxygen, mechanical ventilation, or death. The primary outcome for the combination of ASA and rivaroxaban vs. control is the composite of high flow oxygen, mechanical ventilation, death, or major thrombosis (MI, stroke, ALI, or PI).

*The Inpatient study previously also included a comparison of Interferon-β with control in a 2x2x2 design. The Interferon-β arm was closed to recruitment in November 2020.

Enrollment: 6,667 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Outpatient trial:

Inclusion criteria:

1. Symptomatic and laboratory-confirmed diagnosis of COVID-19.
2. Age ≥ 30 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. Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin).
3. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6,667 participants in 5 patient groups

Colchicine

Experimental group

Description:

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).

Treatment:

Drug: Colchicine

Interferon Beta [This arm is now closed to recruitment]

Experimental group

Description:

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

Treatment:

Drug: Interferon-Beta

Aspirin (ASA)

Experimental group

Description:

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

Treatment:

Drug: Aspirin

Rivaroxaban

Experimental group

Description:

Inpatients Only: 2.5 mg twice daily for 28 days.

Treatment:

Drug: Rivaroxaban

Usual Care (Control)

No Intervention group

Description:

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