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

Primary Purpose

COVID-19, Venous Thromboembolism, Arterial Thrombosis

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Unfractionated Heparin IV

Enoxaparin 1 mg/kg

Clopidogrel

Unfractionated heparin SC

Enoxaparin 40 Mg/0.4 mL Injectable Solution

About this trial

This is an interventional prevention trial for COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Key Exclusion Criteria:

Ongoing (>48 hours) or planned full-dose (therapeutic) anticoagulation for any indication
Ongoing or planned treatment with dual antiplatelet therapy
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 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
History of heparin-induced thrombocytopenia
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

Sites / Locations

Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Full-dose anticoagulation + antiplatelet therapy

Full-dose anticoagulation + no antiplatelet therapy

Prophylactic anticoagulation + antiplatelet therapy

Prophylactic anticoagulation + no antiplatelet therapy

Arm Description

• Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h • Anti-platelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD

• Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h

• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID • Antiplatelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD

• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID

Outcomes

Primary Outcome Measures

Primary endpoint: Venous or arterial thrombotic events

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

Secondary Outcome Measures

Key secondary endpoint: Clinically evident venous or arterial thrombotic events

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

Full Information

NCT ID

NCT04409834

First Posted

May 28, 2020

Last Updated

April 11, 2022

Sponsor

The TIMI Study Group

1. Study Identification

Unique Protocol Identification Number

NCT04409834

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

August 5, 2020 (Actual)

Primary Completion Date

March 10, 2022 (Actual)

Study Completion Date

March 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The TIMI Study Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a multicenter, open-label, 2x2 factorial, 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 for prevention of venous and arterial thrombotic events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19, Venous Thromboembolism, Arterial Thrombosis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

390 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Full-dose anticoagulation + antiplatelet therapy

Arm Type

Experimental

Arm Description

Arm Title

Full-dose anticoagulation + no antiplatelet therapy

Arm Type

Experimental

Arm Description

• Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h

Arm Title

Prophylactic anticoagulation + antiplatelet therapy

Arm Type

Experimental

Arm Description

• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID • Antiplatelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD

Arm Title

Prophylactic anticoagulation + no antiplatelet therapy

Arm Type

Active Comparator

Arm Description

• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID

Intervention Type

Drug

Intervention Name(s)

Unfractionated Heparin IV

Intervention Description

Unfractionated heparin IV targeting an aPTT of 1.5-2.5 times the control

Intervention Type

Drug

Intervention Name(s)

Enoxaparin 1 mg/kg

Intervention Description

Enoxaparin 1 mg/kg SC Q12h

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Intervention Description

Clopidogrel 300 mg PO x1, then clopidogrel 75 mg PO QD

Intervention Type

Drug

Intervention Name(s)

Unfractionated heparin SC

Intervention Description

Unfractionated heparin 5,000 IU SC TID

Intervention Type

Drug

Intervention Name(s)

Enoxaparin 40 Mg/0.4 mL Injectable Solution

Intervention Description

Enoxaparin 40 mg SC QD

Primary Outcome Measure Information:

Title

Primary endpoint: Venous or arterial thrombotic events

Description

Time Frame

28 days or until hospital discharge, whichever earlier

Secondary Outcome Measure Information:

Title

Key secondary endpoint: Clinically evident venous or arterial thrombotic events

Description

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

Time Frame

28 days or until hospital discharge, whichever earlier

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥18 years (male or female) Acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Currently admitted to an intensive care unit (ICU) Key Exclusion Criteria: Ongoing (>48 hours) or planned full-dose (therapeutic) anticoagulation for any indication Ongoing or planned treatment with dual antiplatelet therapy Contraindication to antithrombotic therapy or high risk of bleeding due to conditions including, but not limited to, any of the following: History of intracranial hemorrhage, known CNS tumor or CNS vascular abnormality Active or recent major bleeding within the past 30 days with untreated source Platelet count <70,000 or known functional platelet disorder Fibrinogen <200 mg/dL International normalized ratio (INR) >1.9 History of heparin-induced thrombocytopenia 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc S Sabatine, MD, MPH

Organizational Affiliation

TIMI Study Group

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

David A Morrow, MD, MPH

Organizational Affiliation

TIMI Study Group

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02459

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36036760

Citation

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, Wiviott SD, Van Diepen S, Zainea M, Baird-Zars V, Sabatine MS, Morrow DA; COVID-PACT Investigators. Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT. Circulation. 2022 Nov;146(18):1344-1356. doi: 10.1161/CIRCULATIONAHA.122.061533. Epub 2022 Aug 29.

Results Reference

derived

PubMed Identifier

35474746

Citation

Lee CK, Merriam LT, Pearson JC, Lipnick MS, McKleroy W, Kim EY. Treating COVID-19: Evolving approaches to evidence in a pandemic. Cell Rep Med. 2022 Feb 9;3(3):100533. doi: 10.1016/j.xcrm.2022.100533. eCollection 2022 Mar 15.

Results Reference

derived

PubMed Identifier

35244208

Citation

Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Results Reference

derived

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

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