BivaLirudin versUS Heparin in Extracorporeal Membrane Oxygenation (BLUSH)

• ClinicalTrials.gov Identifier: NCT05959252
• Recruitment Status: Not yet recruiting
• First Posted: July 25, 2023
• Last Update Posted: November 29, 2023
• Sponsor: Sydney Local Health District
• Information provided by (Responsible Party): Sydney Local Health District

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Extracorporeal Membrane Oxygenation Complication	Drug: Unfractionated heparin; Drug: Bivalirudin	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: January 1, 2024
• Estimated Primary Completion Date: September 1, 2025
• Estimated Study Completion Date: May 1, 2026

Arms and Interventions

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 Name: Heparin

Outcome Measures

Primary Outcome Measures :

1. Time in therapeutic range [ Time Frame: 30 days ]
   Proportion of monitoring samples within therapeutic range

Secondary Outcome Measures :

1. Enrolment rate [ Time Frame: 30 days ]
   Enrolment rate
2. Reasons for non-enrolment [ Time Frame: 30 days ]
   Reasons for non-enrolment of eligible patients into the study
3. Crossover between arms [ Time Frame: 30 days ]
   The number of cross over patients between arms of the study
4. Circuit changes [ Time Frame: 30 days ]
   The number of circuit changes and length of circuit life
5. Daily mean aPTT and anti-Xa [ Time Frame: 30 days ]
   Daily mean aPTT and anti-Xa versus stated range
6. Serious adverse events (SAEs) [ Time Frame: 30 days ]
   Number of SAEs
7. Protocol violations [ Time Frame: 30 days ]
   Number of protocol violations
8. Thrombotic events [ Time Frame: 30 days ]
   Number of deep vein thrombosis identified by ultrasound or CT
9. Major bleeding events defined by International Society of Thrombosis and Haemostasis (ISTH) [ Time Frame: 30 days ]
   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)
10. Bleeding events defined by Bleeding Academic Research Consortium (BARC) [ Time Frame: 30 days ]

    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

11. Survival to Intensive care Unit (ICU) discharge [ Time Frame: 30 days ]
    Survival to discharge from ICU (percentage of patients surviving to ICU discharge)
12. Survival to hospital discharge [ Time Frame: 30 days ]
    Hospital Survival (percentage of patients surviving hospital discharge)
13. Blood product usage [ Time Frame: 30 days ]
    Total amount of red blood cells (RBC), platelets, plasma and blood products used during extracorporeal membrane oxygenation support
14. Cost [ Time Frame: 30 days ]
    Total cost of of extracorporeal membrane oxygenation support that includes blood products, blood tests and complications (measured in United States dollars)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, New South Wales

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia, 2050

Contact: Timothy J Southwood +61295156111 timothy.southwood@health.nsw.gov.au

Contact: Mark Dennis, PhD +61295156111 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

Sponsors and Collaborators

Sydney Local Health District

More Information

• Responsible Party: Sydney Local Health District
• ClinicalTrials.gov Identifier: NCT05959252
• Other Study ID Numbers: 2023/ETH00443
• First Posted: July 25, 2023
• Last Update Posted: November 29, 2023
• Last Verified: July 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sydney Local Health District:

ECMO; Bivalirudin; Heparin; Extracorporeal membrane oxygenation

Additional relevant MeSH terms:

Heparin; Calcium heparin; Bivalirudin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors