Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial (COVID-PACT)

TIMI Study Group

Status and phase: Completed; Phase 4

Conditions: COVID-19; Venous Thromboembolism; Arterial Thrombosis

Treatments: Drug: Enoxaparin 1 mg/kg; Drug: Clopidogrel; Drug: Enoxaparin 40 mg SC; Drug: Unfractionated Heparin IV; Drug: Unfractionated heparin SC

Study type: Interventional

Funder types: Other

Identifiers

NCT04409834

CCCTN/TIMI COVID-PACT

Details and patient eligibility

About

The researchers wanted to learn how to help sick patients who are in the hospital because of COVID-19. They are trying to find out the best way that is safe to stop blood clots that could be dangerous from forming in patients with COVID-19. This research study happened at 34 hospitals.

All patients in the study took medicines that help prevent blood clots. These medicines are called blood thinners or anticoagulants. Patients got different amounts of blood thinners to see what works better and is safer. Researchers randomly chose some patients to get more and some to get less.

The researchers also wanted to know if another medicine called clopidogrel can safely help stop blood clots from forming. This kind of medicine helps keep parts of the blood, called platelets, from sticking together. In some patients who did not have other reasons to take a platelet-blocker the researchers randomly chose the patient to take clopidogrel or not. This type of medicine is also called an antiplatelet.

Full description

This is a multicenter, open-label, randomized-controlled trial in critically-ill patients with novel coronavirus disease 2019 (COVID-19) evaluating the efficacy and safety of full-dose vs. standard prophylactic dose anticoagulation and of antiplatelet vs. no antiplatelet therapy (in a nested second randomization) for prevention of venous and arterial thrombotic events. In a subcohort without an ongoing indication for antiplatelet therapy at screening, the second randomization is performed to either antiplatelet or no antiplatelet therapy

Enrollment: 390 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Age ≥18 years (male or female)
2. Acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)
3. Currently admitted to an intensive care unit (ICU)

Key Exclusion Criteria:

1. Ongoing (>48 hours) or planned full-dose (therapeutic) anticoagulation for any indication

2. Ongoing or planned treatment with dual antiplatelet therapy

3. Contraindication to antithrombotic therapy or high risk of bleeding due to conditions including, but not limited to, any of the following:

   1. History of intracranial hemorrhage, known central nervous system (CNS) tumor or CNS vascular abnormality
   2. Active or recent major bleeding within the past 30 days with untreated source
   3. Platelet count <70,000 or known functional platelet disorder
   4. Fibrinogen <200 mg/dL
   5. International normalized ratio (INR) >1.9

4. History of heparin-induced thrombocytopenia

5. Ischemic stroke within the past 2 weeks

Patients who meet the following criterion are excluded from the second randomization (antiplatelet therapy vs. no antiplatelet therapy):

1. Ongoing or planned antiplatelet therapy, including aspirin monotherapy

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 2 patient groups

Full-dose anticoagulation (FDAC)

Experimental group

Description:

* Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the control as per institutional therapeutic target for treatment of venous thrombotic events (VTE) * Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours * With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days

Treatment:

Drug: Enoxaparin 1 mg/kg

Drug: Unfractionated Heparin IV

Drug: Clopidogrel

Standard-dose prophylactic anticoagulation (SDPAC)

Active Comparator group

Description:

* Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if creatinine clearance CrCl \<30 ml/min) * Heparin 5,000 units administered subcutaneous three times daily * With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days

Treatment:

Drug: Enoxaparin 40 mg SC

Drug: Unfractionated heparin SC

Drug: Clopidogrel