Bivalirudin vs Heparin in ECMO Patients

• ClinicalTrials.gov Identifier: NCT03707418
• Recruitment Status: Withdrawn
• First Posted: October 16, 2018
• Last Update Posted: January 19, 2021
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Extracorporeal Membrane Oxygenation Complication	Drug: Heparin Sodium; Drug: Bivalirudin Injection [Angiomax]	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Study Comparing Bivalirudin vs Heparin in Patients With Extracorporeal Membrane Oxygenator (ECMO) Support
• Estimated Study Start Date: April 2021
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: June 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bivalirudin Injection (Angiomax); 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]; Intravenous Bivalirudin titrated to Activated Clotting Time (ACT) levels
Active Comparator: Heparin Sodium; 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; Intravenous Heparin titrated to Partial ThromboplastinTime (PTT) levels

Outcome Measures

Primary Outcome Measures :

1. Number of heparin-induced thrombocytopenia (HIT) events [ Time Frame: 30 days ]
   This will be assessed by serum platelet factor 4 antibody level
2. Number of Cross-overs between arms [ Time Frame: 30 days ]

   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.

3. Number of circuit failures requiring a circuit exchange [ Time Frame: 30 days ]
   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
4. Thrombotic events [ Time Frame: 30 days ]
   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
5. Bleeding events [ Time Frame: 30 days ]
   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
6. Renal failure [ Time Frame: 30 days ]
   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
7. Number of Transfusions [ Time Frame: 30 days ]
   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
8. Number of emergent decannulations [ Time Frame: 30 days ]
   This will be assessed by the number of times patient is separated from ECMO
9. Number of patients surviving to discharge [ Time Frame: 30 days ]
   This will be assessed by the number of patients in each arm who survive to discharge

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:

• 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.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Glenn Whitman, M.D.; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03707418
• Other Study ID Numbers: IRB00176475
• First Posted: October 16, 2018
• Last Update Posted: January 19, 2021
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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.: No

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