Covid-19 Associated Coagulopathy

COVID 19 Associated Coagulopathy Clinical Trial

Official title:

COVID-19-associated Coagulopathy: Safety and Efficacy of Prophylactic Anticoagulation Therapy in Hospitalized Adults With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04360824
• Other study ID #: 202004235
• Status: Completed
• Phase: Phase 4
• Start date: May 6, 2020
• Est. completion date: April 16, 2021

Study information

• Verified date: January 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: April 16, 2021
• Est. primary completion date: April 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• COVID 19 Associated Coagulopathy
• COVID-19
• Hemostatic Disorders

Intervention

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).
• 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).

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa
United States	Gundersen Health System	La Crosse	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Iowa

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. doi: 10.1182/asheducation-2016.1.180. — View Citation

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. — View Citation

Outcome

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