Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) Heparin Study

Study Overview
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Brief Summary
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This single-center, open-label study will evaluate the safety and efficacy of subcutaneous heparin anticoagulation compared to the standard of care systemic intravenous anticoagulation during veno-venous extracorporeal membrane oxygenation for respiratory failure.

Detailed Description
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Extracorporeal membrane oxygenation (ECMO) has been increasing used over the past decade as supportive therapy in patients with respiratory failure, in order to avoid life-threatening hypoxemia, in cases otherwise refractory to conventional treatment. Veno-venous ECMO (VV ECMO) removes carbon dioxide and significantly improves oxygenation in patients with severe lung failure. System anticoagulation is provided for patients undergoing ECMO therapy to prevent clot formation in the ECMO circuit cannulas, circuit tubing, centrifugal pump, and/or oxygenator. Heparin is the standard anticoagulant for ECMO therapy. Although technological advancements and increasing clinical experience have made the use of VV ECMO safer, bleeding and thrombosis are common complications accounting for the majority of morbidity and mortality in ECMO-treated patients.The optimal anticoagulation management for patients on VV ECMO is not known. Thrombotic episodes, characterized mainly by circuit-related clotting, have become more manageable with improvements in ECMO circuit technology and heparin-coated lines. The Extracorporeal Life Support Organization (ELSO) guidelines describe bleeding as the most common complication during extracorporeal life support. Bleeding has been reported to occur in as many as 30% of patients receiving ECMO therapy, and depending on the site of the hemorrhagic complication, can be fatal. Bleeding may occur from mucous membranes, the uterus in women in childbearing years, the GI tract, or bleeding into the head or brain parenchyma. Intra-cranial hemorrhage is the most serious and usually extensive and fatal complication.Intra-cranial hemorrhage was identified in more than 40% of non-survivors treated with ECMO during the H1N1 flu outbreak of 2009. Other less serious complications associated with anticoagulation are anemia and the risks associated with transfusions. Review of our own institutional ECMO experience revealed 10 cases of VV ECMO during which anticoagulation had to be held for clinical reasons, all without subsequent increases in thrombotic complications. Identifying the safest approach to anticoagulation is essential to the future management of patients on ECMO support. In this prospective randomized clinical trial, the investigators propose to evaluate the safety and efficacy of subcutaneous heparin anticoagulation compared to the standard of care systemic intravenous anticoagulation in subjects requiring veno-venous extracorporeal membrane oxygenation for respiratory failure.

Official Title
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Single Center Open Label Randomized Study Evaluating Safety and Efficacy of Subcutaneous Heparin Compared to Standard of Care Intravenous Heparin Anticoagulation During Veno-venous Extracorporeal Membrane Oxygenation for Respiratory Failure

Conditions
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ECMO, Heparin, Respiratory Failure

Intervention / Treatment
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* Drug: subcutaneous heparin anticoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Respiratory failure requiring VV-ECMO support Subject or appointed health care proxy/LAR is able to understand and sign the informed consent form Exclusion Criteria: Subject currently enrolled in another interventional research trial History of hypersensitivity/adverse reaction to heparin Proven Heparin induced thrombocytopenia (HIT) History of patent foramen ovale (PFO) Recent surgery or other contraindication to systemic anticoagulation, e.g. intracranial bleed Medical indication other than ECMO for systemic anticoagulation, e.g. pulmonary embolism

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 |
| --- | --- |
| Experimental: subcutaneous heparin anticoagulation<br>Experimental arm | Drug: subcutaneous heparin anticoagulation<br>* The primary objective of this study is to evaluate the safety and efficacy of subcutaneous heparin anticoagulation compared to the standard of care systemic intravenous anticoagulation during veno-venous extracorporeal membrane oxygenation for respiratory failure. Subjects will be prospectively randomized in 1:1 ratio to subcutaneous heparin anticoagulation or systemic intravenous anticoagulation and followed until 1 week after discontinuation from ECMO support.<br>* Other names: systemic intravenous anticoagulation as SOC;|
| No Intervention: systemic intravenous anticoagulation<br>SOC arm | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding complication | Safety will be assessed by incidence of bleeding complication (clinically apparent or need for blood transfusion without identified source) | 1 week | 
| Incidence of thrombotic complications requiring intervention | Safety will be assessed by incidence of thrombotic complications requiring intervention (initiation of systemic anticoagulation or oxygenator exchange) | 1 week | 
| Incidence of deep venous thrombosis | Incidence of deep venous thrombosis as assessed by four extremity venous ultrasound at one week post-decannulation | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Directly related to bleeding and clotting | 1 year |