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

COVID-19 Clinical Trial

— COVID-PACT  

Official title:

A Multicenter, Randomized-Controlled Trial to Evaluate the Efficacy and Safety of Antithrombotic Therapy for Prevention of Arterial and Venous Thrombotic Complications in Critically-Ill COVID-19 Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04409834
• Other study ID #: CCCTN/TIMI COVID-PACT
• Status: Completed
• Phase: Phase 4
• Start date: August 5, 2020
• Est. completion date: March 10, 2022

Study information

• Verified date: December 2023
• Source: The TIMI Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: March 10, 2022
• Est. primary completion date: March 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arterial Thrombosis
• COVID-19
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Unfractionated Heparin IV
Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an aPTT of 1.5-2.5 times the control as per institutional therapeutic target for treatment of VTE
• Enoxaparin 1 mg/kg
Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours
• Clopidogrel
Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily orally on subsequent days
• Unfractionated heparin SC
Heparin 5,000 units administered subcutaneous three times daily
• Enoxaparin 40 mg SC
Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if CrCl<30 ml/min)

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
The TIMI Study Group

Country where clinical trial is conducted

United States, 

References & Publications (1)

Bohula EA, Berg DD, Lopes MS, Connors JM, Babar I, Barnett CF, Chaudhry SP, Chopra A, Ginete W, Ieong MH, Katz JN, Kim EY, Kuder JF, Mazza E, McLean D, Mosier JM, Moskowitz A, Murphy SA, O'Donoghue ML, Park JG, Prasad R, Ruff CT, Shahrour MN, Sinha SS, Wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation	The efficacy of these interventions was analyzed using an unmatched win ratio.; The number of wins was found by comparing every patient in the FDAC (Full-dose anticoagulation) arm to every patient in the SDPAC (Standard dose prophylactic anticoagulation) arm to determine a 'win' and totaling up the number of wins in each arm.; A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite.; Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT.	28 days or until hospital discharge, whichever earlier
Primary	Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy	The efficacy of these interventions was analyzed using an unmatched win ratio.; The number of wins was found by comparing every patient in the Anti-platelet group to every patient in the No Anti-platelet group arm to determine a 'win' and totaling up the number of wins in each arm.; A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite.; Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT.	28 days or until hospital discharge, whichever earlier
Secondary	Clinically Evident Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation	The efficacy of these interventions was analyzed using an unmatched win ratio.; The number of wins was found by comparing every patient in the FDAC (Full-dose anticoagulation) arm to every patient in the SDPAC (Standard dose prophylactic anticoagulation) arm to determine a 'win' and totaling up the number of wins in each arm.; A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite.; Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia.	28 days or until hospital discharge, whichever earlier
Secondary	Clinically Evident Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy	The efficacy of these interventions was analyzed using an unmatched win ratio.; The number of wins was found by comparing every patient in the Anti-platelet group to every patient in the No Anti-platelet group arm to determine a 'win' and totaling up the number of wins in each arm.; A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite.; Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia.	28 days or until hospital discharge, whichever earlier