Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19 (IMPROVE)

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: NCT04367831
Recruitment Status : Recruiting
First Posted : April 29, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Sahil A. Parikh, Columbia University

Brief Summary:
This study is being conducted to assess the effectiveness of intermediate versus prophylactic doses of anticoagulation (blood thinners) in patients critically ill with COVID-19 in the intensive care units (ICUs) throughout the hospital. Anticoagulation is part of the patient's usual standard of care but determining the dose of anticoagulation is based on physician preference. The investigators are conducting this study (a randomized trial with adaptive design employing cluster randomization) with the support of all of the ICUs to collect data in order to determine what should be the standard of care in terms of anticoagulation in these critically ill patients. The patients care will not be altered other than the choice of anticoagulation (both approved and used throughout the hospital as standard of care) based on the ICU bed they are assigned. Patient data will be collected until discharge.

Condition or disease Intervention/treatment Phase
COVID-19 Venous Thromboses Arterial Thrombosis Drug: Enoxaparin Prophylactic Dose Drug: Heparin Infusion Drug: Heparin SC Drug: Enoxaparin/Lovenox Intermediate Dose Phase 4

Detailed Description:
Hemostatic, biomarker, and inflammatory changes are common in severe manifestations of coronavirus disease 2019 (COVID-19).Such factors, as well as the bedridden status and critical illness may constitute a prothrombotic milieu, predisposing to venous and arterial thrombosis. However, the optimal antithrombotic regimen for patients with COVID-19, especially those with severe disease, remains uncertain and is currently an area of active clinical interest. Prophylactic-dose anticoagulation is generally recommended for acutely ill hospitalized patients. However, given the hemostatic abnormalities of severe COVID-19 illness, it is unknown whether more intensive anticoagulation is preferred to reduce the risk of thrombotic events, potentially mitigating microvascular and macrovascular thrombi and even disseminated intravascular coagulation (DIC). Further, the risks of therapeutic dose anticoagulation must be weighed against the bleeding risks inherent to this approach. To address this critical gap in knowledge in an area of clinical equipoise, the investigators plan to conduct a cluster-randomized trial in patients admitted to intensive care units (ICUs) in a large volume academic medical center to select the best anticoagulation intervention.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19: A Cluster Based Randomized Selection Trial (IMPROVE-COVID)
Actual Study Start Date : May 2, 2020
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Intervention arm: intermediate-dose anticoagulation

If estimated glomerular filtration rate (eGFR) ≥ 30 mL/min: enoxaparin 1mg/kg subcutaneous (SC) daily or unfractionated heparin infusion at 10 units/kg/hour with goal anti-Xa 0.1-0.3 U/mL.

If eGFR <30 mL/min or acute kidney injury or CRRT: Unfractionated heparin infusion at 10 units/kg/hour (minimum 500 units/hour if CRRT) with goal anti-Xa 0.1-0.3 U/mL

Drug: Heparin Infusion
Unfractionated heparin infusion at 10 units/kg/hour with goal anti-Xa 0.1 -0.3U/mL.
Other Name: Heparin

Drug: Enoxaparin/Lovenox Intermediate Dose
If estimated glomerular filtration rate (eGFR) ≥ 30 mL/min: enoxaparin 1mg/kg subcutaneous (SC) daily.
Other Name: Lovenox

Active Comparator: Control arm: prophylaxis

Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines):

If eGFR ≥30 mL/min (stable kidney function):

  1. BMI < 40 kg/m2: Enoxaparin 40 mg SC daily
  2. BMI 40 - 50 kg/m2: Enoxaparin 40 mg SC q12h
  3. BMI > 50 kg/m2: Enoxaparin 60 mg SC q12h

If eGFR < 30 mL/min or acute kidney injury:

  1. 50-120 kg: Unfractionated heparin 5000 units SC q8h
  2. >120 kg: Unfractionated heparin 7500 units SC q8h

If CRRT: Unfractionated heparin infusion pre-filter at 500 units/hour

Drug: Enoxaparin Prophylactic Dose

Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines):

If eGFR ≥30 mL/min (stable kidney function):

  1. BMI < 40 kg/m2: Enoxaparin 40 mg SC daily
  2. BMI 40 - 50 kg/m2: Enoxaparin 40 mg SC q12h
  3. BMI > 50 kg/m2: Enoxaparin 60 mg SC q12h
Other Name: Lovenox

Drug: Heparin SC
Unfractionated heparin at 5000-7500 units subcutaneous (SC) every 8 hours.
Other Name: Heparin




Primary Outcome Measures :
  1. Total Number of Patients with Clinically Relevant Venous or Arterial Thrombotic Events in ICU [ Time Frame: Discharge from ICU or 30 days ]
    Composite of being alive and without clinically-relevant venous or arterial thrombotic events at discharge from ICU (without transfer to another ICU or palliative care unit/hospice) or at 30 days (if ICU duration lasted 30 days or longer).


Secondary Outcome Measures :
  1. Total Number of Patients with In hospital Clinically Relevant Venous or Arterial Thrombotic Events [ Time Frame: Discharge from hospital or 30 days ]
    Composite of being alive and without clinically-relevant venous or arterial thrombotic events at discharge from ICU (without transfer to another ICU or palliative care unit/hospice) or at 30 days (if ICU duration lasted 30 days or longer).

  2. ICU Length of Stay [ Time Frame: Discharge from ICU or 30 days ]
    Length of stay measured in days.

  3. Total Number of Patients with the Need for Renal Replacement Therapy in the ICU [ Time Frame: Discharge from hospital or 30 days ]
    The impact of intermediate-dose anti-coagulation compared with prophylactic anti-coagulation on rates of acute kidney injury and renal recovery in the ICU will be measured with the total number of patients who need of renal replacement therapy in the ICU.

  4. Total Number of Patients with Major bleeding in the ICU [ Time Frame: Discharge from hospital or 30 days ]
    Major bleeding will be assessed by BARC criteria, also explored by International Society on Thrombosis and Haemostasis (ISTH) and Thrombolysis in Myocardial Infarction (TIMI) criteria.

  5. Hospital Length of Stay [ Time Frame: Discharge from hospital or 30 days ]
    Length of stay measured in days.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR)
  • New admission to eligible CUIMC ICUs within 5 days

    • Transfer from nonparticipating to participating ICU is eligible if otherwise meets eligibility criteria.
    • Patients transferred between participating ICUs will maintain initial treatment assignment.
    • Patients not on therapeutic anticoagulation and who were already admitted to participating ICU within 5 days of trial initiation are additionally eligible.

Exclusion Criteria:

  • Weight under 50kg
  • Contraindication to anticoagulation in the opinion of the treating clinician including

    • overt bleeding
    • platelet count <50,000
    • Bleeding Academic Research Consortium (BARC) major bleeding in the past 30 days
    • Gastrointestinal (GI) bleeding within 3 months
    • history of intracranial hemorrhage
    • Ischemic stroke within the past 2 weeks
    • craniotomy/major neurosurgery within the past 30 days
    • cardiothoracic surgery within the past 30 days
    • intra-abdominal surgery within 30 days prior to enrollment
    • Head or spinal trauma in the last months
    • History of uncorrected cerebral aneurysm or arteriovenous malformation (AVM)
    • Intracranial malignancy
    • Presence of an epidural or spinal catheter
    • Recent major surgery within the last 14 days
    • Decrease in hemoglobin >3 g/dL over the last 24 hours
    • Allergic reaction to anticoagulants (e.g. Heparin Induced Thrombocytopenia) as documented in the electronic health records. Extracorporeal membrane oxygenation (ECMO) support or other mechanical circulatory support.
  • Severe chronic liver dysfunction (history of portosystemic hypertension (HTN), esophageal varices, or Child-Pugh class C or above or similar Model For End-Stage Liver Disease (MELD) scores), abnormality in liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin) 5 times greater than upper normal limit.
  • A history of congenital bleeding diatheses or anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia)
  • Treating physician preference for therapeutic anticoagulation
  • Enrollment in other concurrent trials related to anticoagulant or antiplatelet therapy
  • Existing treatment with therapeutic anticoagulation during the previous 7 days of hospitalization prior to ICU admission (e.g. for venous thromboembolism (VTE), atrial fibrillation, mechanical valve, etc).
  • Do-not-resuscitate (DNR) /do-not-intubate (DNI) or comfort measures only (CMO) orders prior to randomization.

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): NCT04367831


Contacts
Layout table for location contacts
Contact: Sahil Parikh, MD 212-305-7060 sap2196@cumc.columbia.edu
Contact: Kate Dalton 347-514-3366 deb2114@cumc.columbia.edu

Locations
Layout table for location information
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lauren Privitera, MPH    347-271-0901    lp2183@cumc.columbia.edu   
Principal Investigator: Sahil Parikh, MD         
Sponsors and Collaborators
Columbia University
Investigators
Layout table for investigator information
Study Chair: Ajay Kirtane, MD Columbia University
Layout table for additonal information
Responsible Party: Sahil A. Parikh, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT04367831    
Other Study ID Numbers: AAAS8980
First Posted: April 29, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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.: Yes
Keywords provided by Sahil A. Parikh, Columbia University:
COVID-19
coronavirus
anticoagulation
Additional relevant MeSH terms:
Layout table for MeSH terms
Thrombosis
Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Heparin
Calcium heparin
Enoxaparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action