Bivalirudin vs Heparin in ECMO Patients

Study Overview
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Brief Summary
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This is an open label, randomized study comparing the clinical outcomes of unfractionated Heparin and Bivalirudin for anticoagulation in adult subjects requiring ECMO support.

Detailed Description
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This open label randomized study will compare the clinical outcomes of patients on ECMO who are anticoagulated with Heparin and Bivalirudin. Patients will be anticoagulated with a heparin bolus at the commencement of ECMO per standard of care, as there will be insufficient time to randomize these frequently emergent patients. Consent for the study will be obtained from a legally authorized representative Prior to starting a continuous infusion of maintenance anticoagulation, patients will be randomized to bivalirudin or heparin. Outcome measures are bleeding, thrombosis, development of Heparin Induced thrombocytopenia, number of cross-overs between the two research arms, circuit failures, decannulation, deaths and discharges from hospital.

Official Title
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A Randomized Study Comparing Bivalirudin vs Heparin in Patients With Extracorporeal Membrane Oxygenator (ECMO) Support

Conditions
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Extracorporeal Membrane Oxygenation Complication

Intervention / Treatment
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* Drug: Heparin Sodium
* Drug: Bivalirudin Injection [Angiomax]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients on veno-arterial (VA) or veno-venous (VV)ECMO Exclusion Criteria: Patient or surrogate decision makers cannot provide informed consent. Patients who have intolerance to either heparin or bivalirudin Patients who received any form of thrombolytic therapy within the past 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bivalirudin Injection (Angiomax)<br>This arm will receive intravenous Bivalirudin for ECMO anticoagulation for the extent of ECMO support or 7 days whichever comes first | Drug: Bivalirudin Injection [Angiomax]<br>* Intravenous Bivalirudin titrated to Activated Clotting Time (ACT) levels<br>|
| Active Comparator: Heparin Sodium<br>This arm will receive intravenous Heparin Sodium for ECMO anticoagulation for the extent of ECMO support or 7 days whichever comes first | Drug: Heparin Sodium<br>* Intravenous Heparin titrated to Partial ThromboplastinTime (PTT) levels<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of heparin-induced thrombocytopenia (HIT) events | This will be assessed by serum platelet factor 4 antibody level | 30 days | 
| Number of Cross-overs between arms | This will be assessed by number of cross over of patients from one arm to the other anti-coagulation arm for any particular clinical reason. Crossover patients will remain in the study and we will continue to collect protocol driven data. These patients will be analyzed separately from those with no cross-over. | 30 days | 
| Number of circuit failures requiring a circuit exchange | Will be determined by total number of circuit exchanges needed in ECMO circuit due to thrombosis. Circuit exchanges may be done due to lack of adequate gas exchange or increased resistance pre and post oxygenator >50mmHg, circuit thrombosis or failure requiring emergent decannulation | 30 days | 
| Thrombotic events | Collect number of thrombotic events, defined as any of the following events; embolic strokes, embolic end-organ ischemia, embolic ischemia to limbs, deep vein thrombosis or venous thromboembolism, Oxygenator effectiveness measured by resistance, Alveolar-arterial oxygen gradient and carbon dioxide elimination | 30 days | 
| Bleeding events | Will be assessed by the total number of one or more of the following: Chest tube output of blood, number of take-backs to operating room for bleeding, number of Hemorrhagic strokes, Gastrointestinal bleeding, Retroperitoneal hemorrhage, number of cessations of anticoagulation for refractory bleeding and any use of antifibrinolytics or factor VII | 30 days | 
| Renal failure | Defined as initiation of renal replacement therapy for kidney injury that develops on ECMO or increase in serum creatinine by more than 2 times its baseline or decrease in Glomerular Filtration Rate by more than 50% or urine output less than 0.3 mL/kg/hr. We will determine the number of patients with renal failure | 30 days | 
| Number of Transfusions | This will be assessed by any of the following: number of utilizations of packed red blood cells and utilization of fresh frozen plasma, utilization of platelets, utilization of cryoprecipitate, utilization of anti-thrombin III, utilization of factor VII, utilization of prothrombin complex concentrate | 30 days | 
| Number of emergent decannulations | This will be assessed by the number of times patient is separated from ECMO | 30 days | 
| Number of patients surviving to discharge | This will be assessed by the number of patients in each arm who survive to discharge | 30 days |