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Full Dose Heparin Vs. Prophylactic Or Intermediate Dose Heparin in High Risk COVID-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04401293
Recruitment Status : Recruiting
First Posted : May 26, 2020
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Alex Spyropoulos, Northwell Health

Brief Summary:
The aim of this study is to test the hypothesis that prophylaxis of severe COVID-19 patients with treatment dose LMWH leads to better thromboembolic-free outcomes and associated complications during hospitalization than prophylaxis with institutional standard of care with prophylactic to intermediate-doses of UFH or LMWH

Condition or disease Intervention/treatment Phase
Sars-CoV2 COVID Drug: Enoxaparin Drug: Prophylactic/Intermediate Dose Enoxaparin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Due to the pragmatic nature of this study "open-label multi-center randomized active control trial" with pseudo-blinding mechanisms at the time of randomization the study subject and corresponding Site PIs will be blinded (unaware of specific treatment arm the patient is assigned to i.e. Arm 0 or Arm 1). The study pharmacists as well as data extractors and designated randomization personnel (i.e. research coordinators and/or research nurses performing the randomization process) will be un-blinded (aware of specific treatment arm the patient is assigned to i.e. Arm 0 or Arm 1). At the time of subject randomization study subjects will be stratified to either ICU level of care vs. Non-ICU level of care.
Primary Purpose: Treatment
Official Title: Systemic Anticoagulation With Full Dose Low Molecular Weight Heparin (LMWH) Vs. Prophylactic or Intermediate Dose LMWH in High Risk COVID-19 Patients (HEP-COVID Trial)
Actual Study Start Date : April 26, 2020
Estimated Primary Completion Date : October 22, 2020
Estimated Study Completion Date : April 26, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Full Dose LMWH anticoagulation therapy
Subjects in this study arm will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin). Enoxaparin 1mg/kg SQ BID for CrCl ≥ 30ml/min (or Enoxaparin 0.5mg/kg SQ BID for CrCl ≥ 15ml/min and < 30ml/min) during the course of their hospitalization.
Drug: Enoxaparin
Full Dose LMWH anticoagulation therapy

Active Comparator: Prophylactic/Intermediate Dose LMWH or UFH therapy
Subjects in this study arm will be treated with Local institutional standard-of-care for prophylactic-dose or intermediate-dose UFH or LMWH. Regimens allowed are UFH up to 22,500 IU daily in BID or TID doses (i.e. UFH 5000 IU SQ BID/TID or 7500 IU BID/TID), enoxaparin 30mg and 40mg SQ QD or BID (the use of weight-based enoxaparin i.e. 0.5mg/kg SQ BID for this arm is acceptable but strongly discouraged), dalteparin 2500IU or 5000IU QD.
Drug: Prophylactic/Intermediate Dose Enoxaparin
Prophylactic/Intermediate Dose LMWH or UFH therapy
Other Names:
  • Unfractionated heparin
  • dalteparin




Primary Outcome Measures :
  1. Composite outcome of arterial thromboembolic events, venous thromboembolic events and all-cause mortality at Day 30 ± 2 days. [ Time Frame: Day 30 ± 2 days ]
    Risk of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Day 30 ± 2 days.


Secondary Outcome Measures :
  1. Major bleeding [ Time Frame: Day 30 ± 2 days ]
    Risk of major bleeding defined using the International Society of Thrombosis and Haemostasis (ISTH) criteria

  2. Composite outcome of arterial thromboembolic events, venous thromboembolic events and all-cause mortality at Hospital Day 10 + 4 [ Time Frame: Day 10 + 4 ]
    The composite of arterial thromboembolic events (including myocardial infarction, stroke, systemic embolism), venous thromboembolism (including symptomatic deep vein thrombosis (DVT) of the upper or lower extremity, asymptomatic proximal DVT of the lower extremity, non-fatal pulmonary embolism (PE)), and all-cause mortality at Hospital Day 10 + 4

  3. Sepsis-induced coagulopathy (SIC) score [ Time Frame: Day 30 ± 2 days. ]

    Sepsis-induced coagulopathy (SIC) score based on ISTH guidelines.

    • Platelets, K/uL (thousands per microliter) [0-2]
    • INR (International Normalized Ratio) [0-2]
    • D-Dimer Levels, ng/mL [0-3]
    • Fibrinogen, mg/dL [0-1]

    Calculated (SIC) scores greater or equal to 4 predicted higher mortality rates within 30 days and greater risk of pulmonary embolism.


  4. Progression to Acute Respiratory Distress Syndrome (ARDS) [ Time Frame: Day 30 ± 2 days. ]
    Progression to Acute Respiratory Distress Syndrome (ARDS) based on monitoring of patient conditions.

  5. Need for Intubation [ Time Frame: Day 30 ± 2 days. ]
    Need for Intubation will be based on monitoring of patient conditions.

  6. Re-hospitalization [ Time Frame: Day 30 ± 2 days. ]
    Need for Re-hospitalization will be based on monitoring of patient conditions.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
  2. Understands and agrees to comply with planned study procedures.
  3. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
  4. Subject consents to randomization within 72 hours of hospital admission or transfer from another facility within 72 hours of index presentation.
  5. Subjects with a positive COVID-19 diagnosis by nasal swab or serologic testing.
  6. Hospitalized with a requirement for supplemental oxygen.
  7. Have:

    • Either a D- Dimer > 4.0 X ULN, OR
    • Sepsis-induced coagulopathy (SIC) score of ≥4

Exclusion Criteria:

  1. Indications for therapeutic anticoagulation
  2. Absolute contraindication to anticoagulation including:

    1. active bleeding,
    2. recent (within 1 month) history of bleed,
    3. dual (but not single) antiplatelet therapy,
    4. active gastrointestinal and intracranial cancer,
    5. a history of bronchiectasis or pulmonary cavitation,
    6. Hepatic failure with a baseline INR > 1.5,
    7. CrCl < 15ml/min,
    8. a platelet count < 25,000,
    9. a history of heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies,
    10. contraindications to enoxaparin including a hypersensitivity to enoxaparin sodium, hypersensitivity to heparin or pork products, hypersensitivity to benzyl alcohol,
    11. pregnant female,
    12. inability to give or designate to give informed consent,
    13. participation in another blinded trial of investigational drug therapy for COVID-19

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401293


Contacts
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Contact: Damian N Inlall, CCRC (516) 600-1482 dinlall@northwell.edu
Contact: Dimitrios Giannis, MD (516) 600-1434 dgiannis@northwell.edu

Locations
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United States, New Jersey
Beth Israel Newark Recruiting
Newark, New Jersey, United States, 07112
Contact: Kevin Molina    973-926-8451    kevin.molina@rwjbh.org   
Principal Investigator: Marc Cohen, MD         
United States, New York
Southside Hospital Recruiting
Bay Shore, New York, United States, 11706
Contact: Barbara Shannon, RN    631-968-3016    bshannon@northwell.edu   
Contact: Lisa Lumley, RN    631-647-3840    llumley@northwell.edu   
Sub-Investigator: Gulru Sharifova, MD         
Sub-Investigator: Aaron Harrison, MD         
Sub-Investigator: Luis Gruberg, MD         
Sub-Investigator: Puneet Gandotra, MD         
Huntington Hospital Recruiting
Huntington, New York, United States, 11743
Contact: Dana Kuziw, RN    631-351-2798    dkuziw@northwell.edu   
Contact: Jane Hubert, RN    631-351-2798    jhubert@northwell.edu   
Sub-Investigator: Paul Maccaro, MD         
Sub-Investigator: Adrian Popp, MD         
Sub-Investigator: George Surguladze, MD         
Sub-Investigator: Cynthia Price, NP         
Lenox Hill Hospital Recruiting
New York, New York, United States, 10075
Contact: Christina Brennan, MD    516-881-7083    cbrennan@northwell.edu   
Sub-Investigator: Andrea Mignatti, MD         
Sub-Investigator: Eugenia Gianos, MD         
Sub-Investigator: Jeremy Jacobson, MD         
Sub-Investigator: Nazish Ilyas, MD         
Long Island Jewish Medical Center Recruiting
Queens, New York, United States, 11040
Contact: Richard Dima, MD    516-881-7064    rdima@northwell.edu   
Sub-Investigator: Mark Goldin, MD         
Sub-Investigator: Janice Wang, MD         
Sub-Investigator: Negin Hajizadeh, MD         
Sub-Investigator: Mangala Narasimhan, MD         
Staten Island University Hospital Recruiting
Staten Island, New York, United States, 10309
Contact: Melissa Panzo, RN    718-226-6629    mpanzo1@northwell.edu   
Contact: Sean Taylor    718-226-6591    staylor12@northwell.edu   
Sub-Investigator: Wassim Diab, MD         
Sub-Investigator: John Flynt, MD         
Sub-Investigator: Phyllis Suen, MD         
Sub-Investigator: Michael Krzyzak, MD         
Sponsors and Collaborators
Northwell Health
Investigators
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Principal Investigator: Alex C Spyropoulos, MD Northwell Health
Additional Information:
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Responsible Party: Alex Spyropoulos, System Director - Anticoagulation and Clinical Thrombosis Services Northwell Health at Lenox Hill Hospital, Northwell Health
ClinicalTrials.gov Identifier: NCT04401293    
Other Study ID Numbers: 20-0340
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Alex Spyropoulos, Northwell Health:
COVID-19
Anticoagulation
Heparin
Coronavirus
Thrombosis
Additional relevant MeSH terms:
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Heparin
Enoxaparin
Calcium heparin
Dalteparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action