- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04367831
Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19 (IMPROVE)
Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19: A Cluster Based Randomized Selection Trial (IMPROVE-COVID)
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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New York
-
New York, New York, United States, 10032
- Columbia University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / 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 |
Unfractionated heparin infusion at 10 units/kg/hour with goal anti-Xa 0.1 -0.3U/mL.
Other Names:
If estimated glomerular filtration rate (eGFR) ≥ 30 mL/min: enoxaparin 1mg/kg subcutaneous (SC) daily.
Other Names:
|
Active Comparator: Control arm: prophylaxis
Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines): If eGFR ≥30 mL/min (stable kidney function):
If eGFR < 30 mL/min or acute kidney injury:
If CRRT: Unfractionated heparin infusion pre-filter at 500 units/hour |
Prophylactic dose anticoagulation (per Columbia University Irving Medical Center (CUIMC) Guidelines): If eGFR ≥30 mL/min (stable kidney function):
Other Names:
Unfractionated heparin at 5000-7500 units subcutaneous (SC) every 8 hours.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Discharge from ICU or 30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
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Discharge from hospital or 30 days
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ICU Length of Stay
Time Frame: Discharge from ICU or 30 days
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Length of stay measured in days.
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Discharge from ICU or 30 days
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Total Number of Patients with the Need for Renal Replacement Therapy in the ICU
Time Frame: Discharge from hospital or 30 days
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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.
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Discharge from hospital or 30 days
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Total Number of Patients with Major bleeding in the ICU
Time Frame: Discharge from hospital or 30 days
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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.
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Discharge from hospital or 30 days
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Hospital Length of Stay
Time Frame: Discharge from hospital or 30 days
|
Length of stay measured in days.
|
Discharge from hospital or 30 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Ajay Kirtane, MD, Columbia University
Publications and helpful links
General Publications
- 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.
- 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.
- Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- Embolism and Thrombosis
- COVID-19
- Thrombosis
- Venous Thrombosis
- Thromboembolism
- Molecular Mechanisms of Pharmacological Action
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Anticoagulants
- Heparin
- Enoxaparin
- Calcium heparin
- Enoxaparin sodium
Other Study ID Numbers
- AAAS8980
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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