Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial
Condition: COVID-19; Venous Thromboembolism; Arterial Thrombosis
MeSH terms: COVID-19; Thrombosis; Thromboembolism; Venous Thromboembolism
Intervention: Unfractionated Heparin IV; Enoxaparin 1 mg/kg; Clopidogrel; Unfractionated heparin SC; Enoxaparin 40 mg SC
Intervention description: 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 administered subcutaneously (SC) every 12 hours; Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily orally on subsequent days; Heparin 5,000 units administered subcutaneous three times daily; Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if CrCl<30 ml/min)
Intervention MeSH terms: Heparin; Calcium heparin; Enoxaparin; Enoxaparin sodium; Clopidogrel
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
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)
Masking: None (Open Label)
Enrollment: 390.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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