Covid-19 Associated Coagulopathy
Condition: COVID 19 Associated Coagulopathy
MeSH terms: COVID-19; Hemostatic Disorders; Blood Coagulation Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      This prospective, randomized, open-label, multi-center interventional study is designed to
      compare the safety and efficacy of two LMWH dosing protocols in patients admitted to the
      University of Iowa Hospitals with COVID-19 who meet the modified ISTH Overt DIC criteria
      score ≥3. Patients will be randomized to standard prophylactic dose LMWH (standard of care
      arm) or intermediate-dose LMWH (intervention arm).
    

Detailed description: 
      Potentially eligible patients will be identified by a healthcare professional per
      institutional policy on privacy. The healthcare professional will assess the eligibility of
      the patient by performing a chart review which will include laboratory results and weight as
      measured on admission to the hospital. After obtaining verbal consent from the patient to be
      contacted for the study, a member of the research staff will approach the patient to be part
      of the study. The research staff will obtain informed consent from the patient/LAR before
      collecting any data and performing any procedures.

      5.2 Trial interventions

      As standard of care, hospitalized patients with confirmed COVID-19 will be monitored for
      coagulopathy. Daily blood tests for platelet count, prothrombin time, D-Dimer, and fibrinogen
      and weekly thromboelastography will be obtained, and a daily Modified ISTH Overt DIC score
      will be calculated (Exhibit 1). Only patients meeting all inclusion and exclusion criteria
      will be asked to participate in the trial. Patients will be randomized to one of two arms:

        1. Patients randomized to the standard of care arm will receive standard prophylactic dose
           enoxaparin (40 mg subcutaneously daily if BMI <30 kg/m2; 30 mg subcutaneously twice
           daily or 40 mg subcutaneously twice daily if BMI ≥ 30 kg/m2).

        2. Patients randomized to the intervention arm will receive intermediate-dose enoxaparin (1
           mg/kg Subcutaneously daily if BMI <30 kg/m2 or 0.5 mg/kg Subcutaneously twice daily if
           BMI ≥ 30 kg/m2), with doses rounded up to the nearest dose syringe in hospitalized
           patients with laboratory confirmed SARS CoV-2 infection.

      5.3 Dose Modifications

        1. Enoxaparin will be held if platelets decrease to <25,000/mm3. Enoxaparin will resume
           once platelets increase to ≥25,000/ mm3.

        2. Enoxaparin will be held if fibrinogen is <50 mg/dL. Enoxaparin will resume once
           fibrinogen increases to ≥50 mg/dL.

        3. Enoxaparin will be held if estimated Creatinine clearance < 15 ml/min calculated by the
           modified Cockcroft and Gault formula and resumed once the Creatinine Clearance is ≥15
           ml/min.

        4. Enoxaparin will be held if there is a clinical suspicion for heparin induced
           thrombocytopenia.

        5. Enoxaparin dose will be reduced by 25% if Creatinine Clearance ≥15 and <30 ml/min
           calculated by the modified Cockcroft and Gault formula and increased once the estimated
           Creatinine Clearance is ≥30 ml/min in both the arms.

      All participating patients will continue the assigned doses of enoxaparin until hospital
      discharge or until a clinical event occurs requiring either discontinuation of
      anticoagulation therapy or full therapeutic dose anticoagulation therapy.
    

Intervention name(s): Intermediate dose thromboprophylaxis; Standard of Care thromboprophylaxis
Intervention type(s): Drug; Drug
Intervention description(s): 2) Patients randomized to the intervention arm will receive intermediate-dose enoxaparin (1 mg/kg Subcutaneously daily if BMI<30kg/m2 or 0.5 mg/kg Subcutaneously twice daily if BMI ≥ 30kg/m2).; Patients randomized to the standard of care arm will receive standard prophylactic dose enoxaparin (40 mg subcutaneously daily if BMI <30kg/m2 and 30 mg subcutaneously twice daily or 40 mg subcutaneously twice daily if BMI ≥ 30 kg/m2).
Other intervention name(s): intermediate dose Enoxaparin
Intervention MeSH terms: Enoxaparin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a multi-center, randomized, open-label study comparing standard prophylactic dose enoxaparin (40 mg SC daily or 30 or 40 mg SC twice daily if BMI ≥30kg/m2; standard of care arm) versus intermediate-dose enoxaparin (1 mg/kg SC daily or 0.5 mg/kg SC twice daily if BMI≥30kg/m2; intervention arm) in hospitalized patients with laboratory-confirmed SARS-CoV-2 infection.
Masking: None (Open Label)
Primary purpose: Treatment