Covid-19 Associated Coagulopathy

NCT04360824 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 202004235
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 2

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).

Conditions

COVID 19 Associated Coagulopathy

Outcome Measures

Primary Outcomes (1)

• Mortality

  All-cause mortality

  30 Days post intervention

Secondary Outcomes (5)

• Number of Participants With Acute Kidney Injury

  30 days post intervention

• Number of Participants With Arterial Thrombosis

  30 Days post intervention

• Number of Participants With Venous Thrombosis

  30 Days post intervention

• Number of Participants With Major Bleeding

  30 Days post intervention

• Number of Participants With Minor Bleeding

  30 Days post intervention

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

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

Interventional

OTHER

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

Interventions

Intermediate dose thromboprophylaxis DRUG

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).

Also known as: intermediate dose Enoxaparin

Interventional

Standard of Care thromboprophylaxis DRUG

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).

Standard of Care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Laboratory confirmed SARS-CoV-2 infection
• Age ≥18 years
• Requires hospital admission for further clinical management
• Modified ISTH Overt DIC score ≥ 3

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (2)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Gundersen Health System

La Crosse, Wisconsin, 54601, United States

Location

Related Publications (6)

• 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.

  PMID: 32109013 BACKGROUND

• 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.

  PMID: 32073213 BACKGROUND

• 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.

  PMID: 27913478 BACKGROUND

• Eustes AS, Palani Kumar MK, Peterson JA, Mast AE, Lentz SR, Dayal S. Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes. Blood Vessel Thromb Hemost. 2025 Apr 29;2(3):100071. doi: 10.1016/j.bvth.2025.100071. eCollection 2025 Aug.

  PMID: 40765912 DERIVED

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

• Flumignan RL, Tinoco JDS, Pascoal PI, Areias LL, Cossi MS, Fernandes MI, Costa IK, Souza L, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;10(10):CD013739. doi: 10.1002/14651858.CD013739.

  PMID: 33502773 DERIVED

Limitations and Caveats

The trial design was based on data available in early 2020 that suggested a mortality of up to 40% in hospitalized patients with severe COVID-19. Another limitation is that the results cannot be extrapolated to all patients hospitalized with COVID-19, because more than 85% of screened patients did not meet eligibility criteria. Lastly, this study was not designed to examine outcomes beyond 30 days.

Results Point of Contact

• Title: Dr. Usha Perepu
• Organization: University of Iowa Hospitals & Clinics

usha-perepu@uiowa.edu

1-319-356-2195

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponser Investigator

Model Details: 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.

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 24, 2020
• Study Start: May 6, 2020
• Primary Completion: April 16, 2021
• Study Completion: April 16, 2021
• Last Updated: March 1, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)