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).
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.
Drug: Intermediate dose thromboprophylaxis
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).
Other Name: intermediate dose Enoxaparin
Drug: Standard of Care thromboprophylaxis
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).
Inclusion Criteria:
- Laboratory confirmed SARS-CoV-2 infection
- Age ≥18 years
- Requires hospital admission for further clinical management
- Modified ISTH Overt DIC score ≥ 3
Exclusion Criteria:
- Indication for full therapeutic-dose anticoagulation
- Acute venous thromboembolism (deep vein thrombosis or pulmonary embolism) within prior
3 months
- Acute cardiovascular event within prior 3 months
- Acute stroke (ischemic or hemorrhagic) within prior 3 months
- Active major bleeding
- Severe thrombocytopenia (<25,000/mm3)
- Increased risk of bleeding, as assessed by the investigator
- Acute or chronic renal insufficiency with Creatinine Clearance < 30 ml/min calculated
by the modified Cockcroft and Gault formula
- Weight < 40 kg
- Known allergies to ingredients contained in enoxaparin, allergy to heparin products or
history of heparin induced thrombocytopenia
University of Iowa
Iowa City, Iowa, United States
Gundersen Health System
La Crosse, Wisconsin, United States