<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04496362</url>
  </required_header>
  <id_info>
    <org_study_id>018-543</org_study_id>
    <nct_id>NCT04496362</nct_id>
  </id_info>
  <brief_title>Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) Heparin Study</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylor Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single-center, open-label study will evaluate the safety and efficacy of subcutaneous&#xD;
      heparin anticoagulation compared to the standard of care systemic intravenous anticoagulation&#xD;
      during veno-venous extracorporeal membrane oxygenation for respiratory failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Extracorporeal membrane oxygenation (ECMO) has been increasing used over the past decade as&#xD;
      supportive therapy in patients with respiratory failure, in order to avoid life-threatening&#xD;
      hypoxemia, in cases otherwise refractory to conventional treatment. Veno-venous ECMO (VV&#xD;
      ECMO) removes carbon dioxide and significantly improves oxygenation in patients with severe&#xD;
      lung failure. System anticoagulation is provided for patients undergoing ECMO therapy to&#xD;
      prevent clot formation in the ECMO circuit cannulas, circuit tubing, centrifugal pump, and/or&#xD;
      oxygenator. Heparin is the standard anticoagulant for ECMO therapy.&#xD;
&#xD;
      Although technological advancements and increasing clinical experience have made the use of&#xD;
      VV ECMO safer, bleeding and thrombosis are common complications accounting for the majority&#xD;
      of morbidity and mortality in ECMO-treated patients.The optimal anticoagulation management&#xD;
      for patients on VV ECMO is not known. Thrombotic episodes, characterized mainly by&#xD;
      circuit-related clotting, have become more manageable with improvements in ECMO circuit&#xD;
      technology and heparin-coated lines.&#xD;
&#xD;
      The Extracorporeal Life Support Organization (ELSO) guidelines describe bleeding as the most&#xD;
      common complication during extracorporeal life support. Bleeding has been reported to occur&#xD;
      in as many as 30% of patients receiving ECMO therapy, and depending on the site of the&#xD;
      hemorrhagic complication, can be fatal. Bleeding may occur from mucous membranes, the uterus&#xD;
      in women in childbearing years, the GI tract, or bleeding into the head or brain parenchyma.&#xD;
      Intra-cranial hemorrhage is the most serious and usually extensive and fatal&#xD;
      complication.Intra-cranial hemorrhage was identified in more than 40% of non-survivors&#xD;
      treated with ECMO during the H1N1 flu outbreak of 2009. Other less serious complications&#xD;
      associated with anticoagulation are anemia and the risks associated with transfusions. Review&#xD;
      of our own institutional ECMO experience revealed 10 cases of VV ECMO during which&#xD;
      anticoagulation had to be held for clinical reasons, all without subsequent increases in&#xD;
      thrombotic complications.&#xD;
&#xD;
      Identifying the safest approach to anticoagulation is essential to the future management of&#xD;
      patients on ECMO support. In this prospective randomized clinical trial, the investigators&#xD;
      propose to evaluate the safety and efficacy of subcutaneous heparin anticoagulation compared&#xD;
      to the standard of care systemic intravenous anticoagulation in subjects requiring&#xD;
      veno-venous extracorporeal membrane oxygenation for respiratory failure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 10, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of bleeding complication</measure>
    <time_frame>1 week</time_frame>
    <description>Safety will be assessed by incidence of bleeding complication (clinically apparent or need for blood transfusion without identified source)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of thrombotic complications requiring intervention</measure>
    <time_frame>1 week</time_frame>
    <description>Safety will be assessed by incidence of thrombotic complications requiring intervention (initiation of systemic anticoagulation or oxygenator exchange)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of deep venous thrombosis</measure>
    <time_frame>1 week</time_frame>
    <description>Incidence of deep venous thrombosis as assessed by four extremity venous ultrasound at one week post-decannulation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>1 year</time_frame>
    <description>Directly related to bleeding and clotting</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>ECMO</condition>
  <condition>Heparin</condition>
  <condition>Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>subcutaneous heparin anticoagulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>systemic intravenous anticoagulation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>SOC arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>subcutaneous heparin anticoagulation</intervention_name>
    <description>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.</description>
    <arm_group_label>subcutaneous heparin anticoagulation</arm_group_label>
    <other_name>systemic intravenous anticoagulation as SOC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥ 18 years of age&#xD;
&#xD;
          2. Respiratory failure requiring VV-ECMO support&#xD;
&#xD;
          3. Subject or appointed health care proxy/LAR is able to understand and sign the informed&#xD;
             consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject currently enrolled in another interventional research trial&#xD;
&#xD;
          2. History of hypersensitivity/adverse reaction to heparin&#xD;
&#xD;
          3. Proven Heparin induced thrombocytopenia (HIT)&#xD;
&#xD;
          4. History of patent foramen ovale (PFO)&#xD;
&#xD;
          5. Recent surgery or other contraindication to systemic anticoagulation, e.g.&#xD;
             intracranial bleed&#xD;
&#xD;
          6. Medical indication other than ECMO for systemic anticoagulation, e.g. pulmonary&#xD;
             embolism&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gary Schwartz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BSWH</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aayla Jamil</last_name>
    <phone>214-820-1675</phone>
    <email>Aayla.Jamil@BSWHealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lorie Estrada</last_name>
    <email>Lorie.Estrada@BSWHealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Health research institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aayla Jamil</last_name>
      <email>Aayla.Jamil@bswhealth.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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>
    <PMID>27690525</PMID>
  </reference>
  <reference>
    <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>
  </reference>
  <reference>
    <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>
    <PMID>27714705</PMID>
  </reference>
  <reference>
    <citation>ELSO Guidelines for Adult Respiratory Failure August, 2017.</citation>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>January 25, 2023</last_update_submitted>
  <last_update_submitted_qc>January 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No sharing of individual participant data (IPD)</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04496362
org study id: 018-543
nct id: NCT04496362
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of bleeding complication
time frame: 1 week
description: Safety will be assessed by incidence of bleeding complication (clinically apparent or need for blood transfusion without identified source)
measure: Incidence of thrombotic complications requiring intervention
time frame: 1 week
description: Safety will be assessed by incidence of thrombotic complications requiring intervention (initiation of systemic anticoagulation or oxygenator exchange)
measure: Incidence of deep venous thrombosis
time frame: 1 week
description: Incidence of deep venous thrombosis as assessed by four extremity venous ultrasound at one week post-decannulation
measure: Mortality
time frame: 1 year
description: Directly related to bleeding and clotting
arm group label: subcutaneous heparin anticoagulation
arm group type: Experimental
description: Experimental arm
arm group label: systemic intravenous anticoagulation
arm group type: No Intervention
description: SOC arm
intervention type: Drug
intervention name: subcutaneous heparin anticoagulation
description: 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.
arm group label: subcutaneous heparin anticoagulation
other name: systemic intravenous anticoagulation as SOC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary Schwartz, MD
role: Principal Investigator
affiliation: BSWH
last name: Aayla Jamil
phone: 214-820-1675
email: Aayla.Jamil@BSWHealth.org
last name: Lorie Estrada
email: Lorie.Estrada@BSWHealth.org
facility: 
status: Recruiting
contact: 
country: United States
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.
PMID: 27690525
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.
PMID: 27714705
citation: ELSO Guidelines for Adult Respiratory Failure August, 2017.
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
mesh term: Heparin
sharing ipd: No
ipd description: No sharing of individual participant data (IPD)