Clinical trial NCT04409834: Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Venous Thromboembolism
Arterial Thrombosis
Lead sponsor: The TIMI Study Group
Sponsor class: OTHER
First posted: 2020-06-01
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized-controlled trial - 1) full-dose anticoagulation (FDAC) versus standard-dose prophylactic anticoagulation (SDPAC) (pooled across antiplatelet regimens) and in a subset of patients 2) antiplatelet (AP) versus no AP therapy (pooled across anticoagulant regimens)
Primary purpose: PREVENTION

Brief 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.

Detailed 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

Eligibility 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

Primary outcomes:
measure: Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation
timeFrame: 28 days or until hospital discharge, whichever earlier
measure: Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy
timeFrame: 28 days or until hospital discharge, whichever earlier
Secondary outcomes:
measure: Clinically Evident Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation
timeFrame: 28 days or until hospital discharge, whichever earlier
measure: Clinically Evident Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy
timeFrame: 28 days or until hospital discharge, whichever earlier
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: The TIMI Study Group
name: Marc S Sabatine, MD, MPH
role: STUDY_CHAIR
affiliation: The TIMI Study Group
name: David A Morrow, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.