Intermediate or Prophylactic-Dose Anticoagulation for Venous or Arterial Thromboembolism in Severe COVID-19 (IMPROVE)
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ClinicalTrials.gov Identifier: NCT04367831 |
Recruitment Status :
Completed
First Posted : April 29, 2020
Last Update Posted : September 29, 2021
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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 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 94 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 |
Actual Primary Completion Date : | May 12, 2021 |
Actual Study Completion Date : | May 12, 2021 |

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):
If eGFR < 30 mL/min or acute kidney injury:
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):
Other Name: Lovenox Drug: Heparin SC Unfractionated heparin at 5000-7500 units subcutaneous (SC) every 8 hours.
Other Name: Heparin |
- 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).
- 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).
- ICU Length of Stay [ Time Frame: Discharge from ICU or 30 days ]Length of stay measured in days.
- 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.
- 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.
- Hospital Length of Stay [ Time Frame: Discharge from hospital or 30 days ]Length of stay measured in days.

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Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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.

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
United States, New York | |
Columbia University Medical Center | |
New York, New York, United States, 10032 |
Study Chair: | Ajay Kirtane, MD | Columbia University |
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: | September 29, 2021 |
Last Verified: | September 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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 |
COVID-19 coronavirus anticoagulation |
COVID-19 Thrombosis Thromboembolism Venous Thrombosis Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections |
Lung Diseases Respiratory Tract Diseases Embolism and Thrombosis Vascular Diseases Cardiovascular Diseases Heparin Calcium heparin Enoxaparin Enoxaparin sodium Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |