Clinical trial NCT04496362: Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) Heparin Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: ECMO
Heparin
Respiratory Failure
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2020-08-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years of age
2. Respiratory failure requiring VV-ECMO support
3. Subject or appointed health care proxy/LAR is able to understand and sign the informed consent form

Exclusion Criteria:

1. Subject currently enrolled in another interventional research trial
2. History of hypersensitivity/adverse reaction to heparin
3. Proven Heparin induced thrombocytopenia (HIT)
4. History of patent foramen ovale (PFO)
5. Recent surgery or other contraindication to systemic anticoagulation, e.g. intracranial bleed
6. Medical indication other than ECMO for systemic anticoagulation, e.g. pulmonary embolism

Primary outcomes:
measure: Incidence of bleeding complication
timeFrame: 1 week
measure: Incidence of thrombotic complications requiring intervention
timeFrame: 1 week
measure: Incidence of deep venous thrombosis
timeFrame: 1 week
Secondary outcomes:
measure: Mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor Scott & White Health research institute
state: Texas
Study officials:
affiliation: BSWH
name: Gary Schwartz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sklar MC, Sy E, Lequier L, Fan E, Kanji HD. Anticoagulation Practices during Venovenous Extracorporeal Membrane Oxygenation for Respiratory Failure. A Systematic Review. Ann Am Thorac Soc. 2016 Dec;13(12):2242-2250. doi: 10.1513/AnnalsATS.201605-364SR.
citation: Vaugh N, Hernandez O, Estroff J. Extracorporeal Membrane Oxygenation without Anticoagulation in Traumatic Brain Injury. Poster Presentation, American College of Surgeons Texas Chapter State Meeting, February 23-25, 2017, Austin, TX.
citation: Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care. 2016 Dec;6(1):97. doi: 10.1186/s13613-016-0196-7. Epub 2016 Oct 6.
citation: ELSO Guidelines for Adult Respiratory Failure August, 2017.