Covid-19 Associated Coagulopathy

Phase 4

Completed

Conditions: COVID 19 Associated Coagulopathy

Interventions: Drug: Standard of Care thromboprophylaxis
Drug: Intermediate dose thromboprophylaxis

Registration Number: NCT04360824

Lead Sponsor: University of Iowa

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 176

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care thromboprophylaxis	1) 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 ≥ 30kg/m2).
Interventional	Intermediate dose thromboprophylaxis	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 ≥ 30kg/m2).

Primary Outcome Measures

Name	Time	Method
Mortality	30 Days post intervention	All-cause mortality

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Acute Kidney Injury	30 days post intervention	Defined as an estimated creatinine clearance \<30 mL/min
Number of Participants With Arterial Thrombosis	30 Days post intervention	Risk of ischemic stroke, myocardial infarction and/or limb ischemia
Number of Participants With Major Bleeding	30 Days post intervention	Those at risk of ISTH defined major bleeding, such as fatal bleeding, or bleeding into a critical area or organ.
Number of Participants With Venous Thrombosis	30 Days post intervention	Those at risk of symptomatic venous thromboembolism, which is a blood clot in a vein.
Number of Participants With Minor Bleeding	30 Days post intervention	Defined as a bleeding event that did not meet ISTH criteria for major bleeding.