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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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)

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

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Full-dose anticoagulation (FDAC) 		- 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
  • 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
  • Drug: Enoxaparin 1 mg/kg
    Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours
    Other names:
    • Lovenox
  • Drug: Clopidogrel
    Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily orally on subsequent days
    Other names:
    • Plavix
Active Comparator
Standard-dose prophylactic anticoagulation (SDPAC) 		- 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
  • Drug: Clopidogrel
    Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily orally on subsequent days
    Other names:
    • Plavix
  • Drug: Unfractionated heparin SC
    Heparin 5,000 units administered subcutaneous three times daily
  • Drug: Enoxaparin 40 mg SC
    Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if CrCl<30 ml/min)
    Other names:
    • Lovenox

Recruiting Locations

More Details

NCT ID
NCT04409834
Status
Completed
Sponsor
The TIMI Study Group

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.