BivaLirudin versUS Heparin in Extracorporeal Membrane Oxygenation

Study Overview
=================
Brief Summary
-----------------
The goal of this open label randomised clinical trial is to compare Bivalirudin versus Heparin for anticoagulation in patients requiring extracorporeal membrane oxygenation support. The main question it aims to answer are include the ability to maintain anticoagulation within defined therapeutic range, bleeding and thrombotic complications and a comparison of the total cost of anticoagulation care. Participants will be randomised to either anticoagulation with Bivalirudin or anticoagulation with Unfractionated Heparin.

Detailed Description
-----------------
Rationale: Anticoagulation whilst on extracorporeal membrane oxygenation (ECMO) is required. Bleeding and thrombotic complications whilst on ECMO are common and may effect the patient outcome. The optimal anticoagulant for ECMO patients is not clear and there exists no randomised control trial data comparing anticoagulants on ECMO. This Phase 2b trial will provide data to enable larger definitive phase III trials to determine the best anticoagulant whilst on ECMO. Hypothesis: Hypothesis: In adults ECMO patients'; anticoagulation with Bivalirudin results in more samples within therapeutic range than unfractionated Heparin. Total anticoagulation costs with Bivalirudin are similar to unfractionated Heparin. The objectives of this study is to assess anticoagulation protocol of bivalirudin versus unfractionated heparin and assess the to the cost of each protocol.

Official Title
-----------------
BivaLirudin versUS Heparin in ECMO - A Registry-embedded, Randomised, Open Label, Feasibility Trial Comparing Two Anticoagulation Strategies in Patients on Extracorporeal Membrane Oxygenation (ECMO)

Conditions
-----------------
Extracorporeal Membrane Oxygenation Complication

Intervention / Treatment
-----------------
* Drug: Unfractionated heparin
* Drug: Bivalirudin


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA Patients receiving ECMO Age: 18 years or older Ability to randomise the patient within 4 hours of ECMO support initiation EXCLUSION CRITERIA Post-cardiotomy ECMO patients Contraindication to heparin or bivalirudin at time of randomisation e.g., active bleeding Heparin induced thrombotic thrombocytopenia syndrome Where the patient is expected to be disconnected from ECMO in the next day after cannulation. Limitations of care put in place either through patient wishes or the treating medical teams Other reason where the treating physician deems the study is not in the patient's best interest Patients who are suspected or confirmed to be pregnant Inherited bleeding or thrombotic disorders, Systemic Lupus Erythematosus patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<br>Bivalirudin protocol with target activated thromboplastin time (aPTT) of 50-70 seconds | Drug: Bivalirudin<br>* Bivalirudin protocol with target aPTT 50-70 seconds<br>|
| Active Comparator: Unfractionated Heparin<br>Unfractionated heparin protocol with target anti-Xa of 0.3-0.5 IU/mL | Drug: Unfractionated heparin<br>* Unfractionated Heparin protocol with target anti-Xa of 0.3-0.5 IU/mL<br>* Other names: Heparin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in therapeutic range | Proportion of monitoring samples within therapeutic range | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrolment rate | Enrolment rate | 30 days | 
| Reasons for non-enrolment | Reasons for non-enrolment of eligible patients into the study | 30 days | 
| Crossover between arms | The number of cross over patients between arms of the study | 30 days | 
| Circuit changes | The number of circuit changes and length of circuit life | 30 days | 
| Daily mean aPTT and anti-Xa | Daily mean aPTT and anti-Xa versus stated range | 30 days | 
| Serious adverse events (SAEs) | Number of SAEs | 30 days | 
| Protocol violations | Number of protocol violations | 30 days | 
| Thrombotic events | Number of deep vein thrombosis identified by ultrasound or CT | 30 days | 
| Major bleeding events defined by International Society of Thrombosis and Haemostasis (ISTH) | Major bleeding was defined according to the criteria as clinically overt bleeding which was fatal or associated with any of the following: (a) a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells, (b) involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal) | 30 days | 
| Bleeding events defined by Bleeding Academic Research Consortium (BARC) | Number of bleeding events as per BARC Hemorrhagic complications assessed and adapted as per Bleeding Academic Research Consortium (BARC) Type 0: No bleeding Type 1: Bleeding requiring transfusion of packed red blood cells (PRBC) or reduction of UFH Type 2: Bleeding requiring transfusion of PRBC and reduction of UFH Type 3: Life-threatening bleeding requiring, transfusion of PRBC, surgical intervention or discontinuation of ECMO Type 4: Any fatal bleeding | 30 days | 
| Survival to Intensive care Unit (ICU) discharge | Survival to discharge from ICU (percentage of patients surviving to ICU discharge) | 30 days | 
| Survival to hospital discharge | Hospital Survival (percentage of patients surviving hospital discharge) | 30 days | 
| Blood product usage | Total amount of red blood cells (RBC), platelets, plasma and blood products used during extracorporeal membrane oxygenation support | 30 days | 
| Cost | Total cost of of extracorporeal membrane oxygenation support that includes blood products, blood tests and complications (measured in United States dollars) | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bivalirudin, ECMO, Heparin, Extracorporeal membrane oxygenation