BivaLirudin versUS Heparin in Extracorporeal Membrane Oxygenation (BLUSH)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Drug: Bivalirudin; Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
      • Contact: Timothy J Southwood; Phone Number: +61295156111; Email: timothy.southwood@health.nsw.gov.au
      • Contact: Mark Dennis, PhD; Phone Number: +61295156111; Email: mark.dennis@sydney.edu.au
      • Principal Investigator: Timothy J Southwood
      • Sub-Investigator: Elliot Worku
      • Sub-Investigator: Paul Forrest
      • Sub-Investigator: Richard Totaro
      • Sub-Investigator: Lucy Wells
      • Sub-Investigator: Mark Dennis
      • Sub-Investigator: Ru Carey
      • Sub-Investigator: Bruce Cartwright
      • Sub-Investigator: Brian Plunkett
      • Sub-Investigator: Lianne Khoo
      • Sub-Investigator: Anthony Keech
      • Sub-Investigator: Ian Marschner

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bivalirudin; Bivalirudin protocol with target activated thromboplastin time (aPTT) of 50-70 seconds	Drug: Bivalirudin; Bivalirudin protocol with target aPTT 50-70 seconds
Active Comparator: Unfractionated Heparin; Unfractionated heparin protocol with target anti-Xa of 0.3-0.5 IU/mL	Drug: Unfractionated heparin; Unfractionated Heparin protocol with target anti-Xa of 0.3-0.5 IU/mL; 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
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
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
Serious adverse events (SAEs)	Number of SAEs	30 days
Protocol violations	Number of protocol violations	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
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 unfractionated heparin Type 2: Bleeding requiring transfusion of PRBC and reduction of unfractionated heparin Type 3: Life-threatening bleeding requiring, transfusion of PRBC, surgical intervention or discontinuation of ECMO Type 4: Any fatal bleeding	30 days

Collaborators and Investigators

• Sponsor: Sydney Local Health District

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 2, 2023
• First Submitted That Met QC Criteria: July 16, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ECMO; Heparin; Extracorporeal membrane oxygenation; Bivalirudin
• Additional Relevant MeSH Terms: Carbohydrates; Glycosaminoglycans; Polysaccharides; Heparin; bivalirudin
• Other Study ID Numbers: 2023/ETH00443

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No