Covid-19 Associated Coagulopathy
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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:
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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).
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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
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Enoxaparin will be held if platelets decrease to <25,000/mm3. Enoxaparin will resume once platelets increase to ≥25,000/ mm3.
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Enoxaparin will be held if fibrinogen is <50 mg/dL. Enoxaparin will resume once fibrinogen increases to ≥50 mg/dL.
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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.
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Enoxaparin will be held if there is a clinical suspicion for heparin induced thrombocytopenia.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Standard of Care 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). |
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).
|
| Other: Interventional 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). |
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 Names:
|
Outcome Measures
Primary Outcome Measures
- Mortality [30 Days post intervention]
Risk of all-cause mortality
Secondary Outcome Measures
- Major Bleeding [30 Days post intervention]
Risk of ISTH defined major bleeding
- Arterial Thrombosis [30 Days post intervention]
Risk of ischemic stroke, myocardial infarction and/or limb ischemia
- Venous Thromboembolism [30 Days post intervention]
Risk of symptomatic venous thromboembolism
- ICU admission, intubation/ventilation [30 Days post intervention]
duration of intensive care measures
- Packed Red Blood Cell Transfusions [30 Days post intervention]
The number of units of packed red blood cells transfused
- Platelet Transfusions [30 Days post intervention]
The number of units of platelets transfused
- Fresh Frozen Plasma Transfusions [30 Days post intervention]
The number of units of Fresh Frozen Plasma Transfused
- Cryoprecipitate Transfusions [30 Days post intervention]
The number of units of Cryoprecipitate Transfused
- Prothrombin Complex Concentrate Transfusions [30 Days post intervention]
The number of units of Prothrombin Complex ConcentrateTransfused
Other Outcome Measures
- The endogenous thrombin potential will be determined within 24 hours of randomization and weekly for 30 days or until hospital discharge [30 days post intervention]
Will be performed in stored plasma using Calibrated Automated Thrombogram. The endogenous thrombin potential will be calculated in units of nM.Min.
- Plasma levels of cell-free DNA will be determined within 24 hours of randomization and weekly for 30 days or until hospital discharge [30 days post intervention]
These assays will be performed in stored plasma. Quantification of cfDNA will be performed using Qubit dsDNA HS Assay kit. Histones H4, citrullinated-histone and DNA-myeloperoxidase will be measured using commercially available ELISA kit.
- PAI-1 [30 days post intervention]
will be measured in stored plasma using a commercially available ELISA kit.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Laboratory confirmed SARS-CoV-2 infection
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Age ≥18 years
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Requires hospital admission for further clinical management
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Modified ISTH Overt DIC score ≥ 3
Exclusion Criteria:
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Indication for full therapeutic-dose anticoagulation
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Acute venous thromboembolism (deep vein thrombosis or pulmonary embolism) within prior 3 months
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Acute cardiovascular event within prior 3 months
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Acute stroke (ischemic or hemorrhagic) within prior 3 months
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Active major bleeding
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Severe thrombocytopenia (<25,000/mm3)
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Increased risk of bleeding, as assessed by the investigator
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Acute or chronic renal insufficiency with Creatinine Clearance < 30 ml/min calculated by the modified Cockcroft and Gault formula
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Weight < 40 kg
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Known allergies to ingredients contained in enoxaparin, allergy to heparin products or history of heparin induced thrombocytopenia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 2 | Gundersen Health System | La Crosse | Wisconsin | United States | 54601 |
Sponsors and Collaborators
- University of Iowa
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
- Lentz SR. Thrombosis in the setting of obesity or inflammatory bowel disease. Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):180-187. Review.
- Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
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