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

Sponsor

Population Health Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04324463

Collaborator

Bayer (Industry)

6,667

Enrollment

Locations

Arms

29.3

Anticipated Duration (Months)

101

Patients Per Site

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Severe Acute Respiratory Syndrome	Drug: Colchicine Drug: Interferon-Beta Drug: Aspirin Drug: Rivaroxaban	Phase 3

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. 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6667 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-label, parallel group, factorial, randomized controlled trialOpen-label, parallel group, factorial, randomized controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Anti-Coronavirus Therapies to Prevent Progression of COVID-19, a Randomized Trial

Actual Study Start Date :

Apr 21, 2020

Actual Primary Completion Date :

Feb 10, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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 [This arm is now closed to recruitment] 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 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.

Outcome Measures

Primary Outcome Measures

Outpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of hospitalization or death [45 days post randomization]
Outpatient trial - Aspirin vs. control: Time from randomization to first occurrence of the composite of hospitalization, death or major thrombosis (MI, stroke, ALI, or PE) [45 days post randomization]
Inpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or death [45 days post randomization]
Inpatient trial - Aspirin and Rivaroxaban vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, death or major thrombosis (MI, stroke, ALI, or PE) [45 days post randomization]

Secondary Outcome Measures

Outpatient trial - Aspirin vs. control: Time from randomization to first occurrence of any thrombosis (MI, stroke, ALI, PE, or DVT) [45 days post randomization]
Inpatient trial - Colchicine vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or respiratory death [45 days post randomization]
Inpatient trial - Aspirin vs. control: Time from randomization to first occurrence of the composite of high flow oxygen, mechanical ventilation, or respiratory death [45 days post randomization]
Inpatient trial - Aspirin vs. control: Time from randomization to first occurrence of any thrombosis (MI, stroke, ALI, PE, or DVT) [45 days post randomization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Outpatient trial:

Inclusion criteria:

Symptomatic and laboratory-confirmed diagnosis of COVID-19.
Age ≥ 30 years.
High risk: either age ≥70 or 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 criteria:

General: advanced kidney disease; advanced liver disease; pregnancy (known or potential) or lactation.
Colchicine: allergy or planned use; current or planned use of cyclosporine, verapamil, HIV protease inhibitor, azole antifungal, or macrolide antibiotic (except azithromycin).
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:

Symptomatic and laboratory-confirmed diagnosis of COVID-19.
Age ≥18 years.
Within 72 hours (ideally 24 hours) of admission, or worsening clinically.

Exclusion criteria:

General: advanced kidney disease; 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 inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin).
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Adventista de Manaus	Manaus	Amazonas	Brazil
2	Prodal Saude S/A	Salvador	BA	Brazil
3	Hospital das Clinicas de Vitoria (Hospital Universitario Cassiano Antonio Moraes)	Vitoria	ES	Brazil
4	Ubermed Serviços em Saúde Eireli - Hospital São Domingos	Uberaba	MG	Brazil
5	Hospital de Clínicas da Universidade Federal de Uberlândia	Uberlândia	MG	Brazil
6	Hospital Universitario Julio Muller	Cuiabá	Mount	Brazil
7	Instituto Tacchini de Pesquisa em Saude / Hospital Tacchini	Bento Goncalves	Rio Grande Do Sul	Brazil
8	Santa Casa de Votuporanga	Votuporanga	Sao Paulo	Brazil
9	Hospital Universitario Prof. Dr. Horacio Carlos Panepucci da Universidade Federal de Sao Carlos (HU-UFSCar)	São Carlos	SP	Brazil
10	Hospital Alemão Oswaldo Cruz	São Paulo	SP	Brazil
11	CardiAI Inc.	Calgary	Alberta	Canada
12	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8L2X2
13	London Health Sciences Centre	London	Ontario	Canada
14	Southlake Regional Health Centre	Newmarket	Ontario	Canada
15	Halton Healthcare/Oakville Trafalgar Memorial Hospital	Oakville	Ontario	Canada
16	Niagara Health System-St. Catharine's	St. Catharines	Ontario	Canada
17	Toronto Western Hospital Family Health Team	Toronto	Ontario	Canada
18	Windsor Regional Hospital	Windsor	Ontario	Canada
19	Woodstock Hospital	Woodstock	Ontario	Canada
20	CIUSSS de L'est-de-l'ile de Montreal, Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada
21	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec	Canada
22	Biomelab SAS	Barranquilla	Atlantico	Colombia
23	Clinica de la Costa LTDA	Barranquilla	Atlantico	Colombia
24	Instituto de Neumologico del Oriente	Bucaramanga	Santander	Colombia
25	Unicormed	Guayaquil	Guayas	Ecuador
26	Hospital de Especialidades Eugenio Espejo	Quito	Pichincha	Ecuador
27	Hospital Enrique Garces	Quito	Pichincha	Ecuador
28	Hospital General Pablo Arturo Suarez	Quito	Pichincha	Ecuador
29	Oncoambato	Ambato	Tungurahua	Ecuador
30	Giza Chest Hospital	Giza	Cairo	Egypt
31	Abbasia Chest Hospital	Cairo		Egypt
32	Abbasia Fever Hospital	Cairo		Egypt
33	National Hepatology and Tropical Medicine Research Institute	Cairo		Egypt
34	Fayoum University Hospital	Fayoum		Egypt
35	St. John's Medical College and Hospital	Bangalore	Karnataka	India
36	Bharathi Hospital and Research Center	Pune	Maharashtra	India
37	Sanjeevan Hospital	Pune	Maharashtra	India
38	Sidhu Hospital Pvt.Ltd	Doraha	Punjab	India
39	SRM Medical College Hospital & Research Center	Chengalpattu	Tamil Nadu	India
40	AIG Hospital	Hyderabad	Telangana	India
41	KIMS	Secunderabad	Telangana	India
42	Chitwan Medical College	Bharatpur-10	Bagmati	Nepal
43	Sahid Gangalal National Heart Center	Kathmandu	Bagmati	Nepal
44	Province Hospital, Karnali Province	Surkhet	Karnali	Nepal
45	Mechi Zonal Hospital	Bhadrapur	Province No. 1	Nepal
46	Koshi Zonal Hospital	Biratnagar	Province No. 1	Nepal
47	B.P. Koirala Institute of Health Sciences	Kathmandu	Province No.1	Nepal
48	Aga Khan University Hospital	Karachi	Sindh	Pakistan
49	Jinnah Postgraduate Medical Center	Karachi	Sindh	Pakistan
50	Tabba Heart Institute	Karachi	Sindh	Pakistan
51	Philippine General Hospital	Manila	Metro Manila	Philippines
52	State Budgetary Health Care Institution of Sverdlovsk region "Central city clinical hospital # 6 Ekaterinburg"	Ekaterinburg	Sverdlovsk Region	Russian Federation
53	Central City Clinical Hospital No. 24	Yekaterinburg	Sverdlovsk Region	Russian Federation
54	Tver State Medical University	Tver	Tver Oblast	Russian Federation
55	Voronezh State Medical University named after N.N. Burdenko	Voronezh	Voronezh Region	Russian Federation
56	Altai Regional Center for Medical Prevention	Barnaul		Russian Federation
57	City Clinical Hospital No. 15 named after O.M. Filatova	Moscow		Russian Federation
58	National Medical Research Center for Therapy and Preventive Medicine	Moscow		Russian Federation
59	City Clinical Hospital No. 3	Nizhny Novgorod		Russian Federation
60	Rostov State Medical University	Rostov-on-Don		Russian Federation
61	Tiervlei Trial Centre	Cape Town	Western Cape	South Africa
62	University of Cape Town- Groote Schuur Hospital	Cape Town	Western Cape	South Africa
63	TASK Eden	George	Western Cape	South Africa
64	Hatta Hospital	Hatta	Dubai	United Arab Emirates
65	Rashid Hospital, Dubai Health Authority	Dubai		United Arab Emirates
66	Thumbay Hospital Dubai	Dubai		United Arab Emirates

Sponsors and Collaborators

Population Health Research Institute
Bayer

Investigators

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