<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/NCT03255174</url>
  </required_header>
  <id_info>
    <org_study_id>BIOS-16-001</org_study_id>
    <nct_id>NCT03255174</nct_id>
  </id_info>
  <brief_title>The EVARREST® Pediatric Mild or Moderate Liver and Soft Tissue Bleeding Study</brief_title>
  <official_title>A Prospective Study Evaluating the Safety and Effectiveness of EVARREST® Fibrin Sealant Patch in Controlling Mild or Moderate Hepatic Parenchyma or Soft Tissue Bleeding During Open Abdominal, Retroperitoneal, Pelvic and Thoracic (Non-cardiac) Surgery in Pediatric Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ethicon, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ethicon, Inc.</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>
      The objective of this study is to evaluate the safety and hemostatic effectiveness of&#xD;
      EVARREST as an adjunct to controlling mild to moderate soft hepatic parenchyma or soft tissue&#xD;
      bleeding during open hepatic, abdominal, pelvic, retroperitoneal, and thoracic (non-cardiac)&#xD;
      surgery in pediatric population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multicenter, single-arm study evaluating the safety and effectiveness&#xD;
      of EVARREST in controlling mild or moderate bleeding in hepatic parenchyma or soft tissue for&#xD;
      which standard methods of achieving hemostasis are ineffective or impractical.&#xD;
&#xD;
      Eligible subjects will be treated with EVARREST. Subjects will be followed post-operatively&#xD;
      through discharge and at 30 days (+/-14 days) post-surgery.&#xD;
&#xD;
      Enrollment will be staggered by age. The first group will include 31 subjects ≥1 years to &lt;18&#xD;
      years of age and the subsequent group will include 4 subjects from 1 month (≥ 28 days from&#xD;
      birth) to &lt;1 years of age. Ongoing safety assessment will ensure adequate safety monitoring&#xD;
      occur during the staged enrollment.&#xD;
&#xD;
      At least thirty-five (35) qualified pediatric subjects with an appropriate mild or moderate&#xD;
      bleeding TBS will be enrolled in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 20, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute time to hemostasis</measure>
    <time_frame>Intraoperative from TBS identification to the last moment in time at which no detectable bleeding at the TBS is observed</time_frame>
    <description>The absolute time to hemostasis, defined as the absolute time elapsed from TBS identification to the last moment in time at which detectable bleeding at the TBS is observed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemostatic success at 4 minutes</measure>
    <time_frame>Intraoperative, 4 minutes after TBS identification</time_frame>
    <description>Proportion of subjects achieving hemostatic success at 4 minutes following Target Bleeding Site (TBS) identification and no bleeding requiring treatment at the TBS any time prior to final fascial closure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemostatic success at 10 minutes</measure>
    <time_frame>Intraoperative, 10 minutes after TBS identification</time_frame>
    <description>Proportion of subjects achieving hemostatic success at 10 minutes following TBS identification and no bleeding requiring treatment at the TBS any time prior to final fascial closure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>No re-bleeding at the TBS</measure>
    <time_frame>Intraoperative, from TBS identification to final fascial closure</time_frame>
    <description>Proportion of subjects with no re-bleeding at the TBS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events that are potentially related to bleeding at the TBS</measure>
    <time_frame>Intraoperative to 30 (+/- 14) days</time_frame>
    <description>Incidence of adverse events that are potentially related to bleeding at the TBS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events that are potentially related to thrombotic events</measure>
    <time_frame>Intraoperative to 30 (+/- 14) days</time_frame>
    <description>Incidence of adverse events that are potentially related to thrombotic events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of re-treatment at the TBS</measure>
    <time_frame>Intraoperative, from TBS identification to final fascial closure</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>Intraoperative to 30 (+/- 14) days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Controlling Mild to Moderate Bleeding During Surgery</condition>
  <arm_group>
    <arm_group_label>EVARREST® Fibrin Sealant Patch</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EVARREST Fibrin Sealant Patch is a sterile, bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EVARREST® Fibrin Sealant Patch</intervention_name>
    <description>EVARREST Fibrin Sealant Patch is a sterile, bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.</description>
    <arm_group_label>EVARREST® Fibrin Sealant Patch</arm_group_label>
    <other_name>EVARREST</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pediatric subjects aged ≥28 days (≥1 month) to &lt;18 years, requiring non-emergent open&#xD;
             hepatic, abdominal, retroperitoneal, pelvic or thoracic (non-cardiac) surgical&#xD;
             procedures; i) The first 31 subjects to be enrolled will be subjects aged ≥1 years to&#xD;
             &lt;18 years.&#xD;
&#xD;
             ii) The next 4 subjects to be enrolled will be subjects aged ≥28 days to &lt;1 year.&#xD;
&#xD;
          2. The subject's parent/legal guardian must be willing to give permission for the subject&#xD;
             to participate in the trial, and provide written Informed Consent for the subject. In&#xD;
             addition, assent must be obtained from pediatric subjects who possess the intellectual&#xD;
             and emotional ability to comprehend the concepts involved in the trial. If the&#xD;
             pediatric subject is not able to provide assent (due to age, maturity and/or inability&#xD;
             to intellectually and/or emotionally comprehend the trial), the parent/legal&#xD;
             guardian's written Informed Consent for the subject will be acceptable for the subject&#xD;
             to be included in the study.&#xD;
&#xD;
          3. Presence of an appropriate mild or moderate bleeding soft tissue or hepatic parenchyma&#xD;
             Target Bleeding Site (TBS) identified intra-operatively by the surgeon;&#xD;
&#xD;
          4. Ability to firmly press trial treatment at TBS until 4 minutes after TBS&#xD;
             identification.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with known intolerance to blood products or to one of the components of the&#xD;
             study product or is unwilling to receive blood products;&#xD;
&#xD;
          2. Female subjects, of childbearing age (i.e. adolescent), who are pregnant or nursing;&#xD;
&#xD;
          3. Subject is currently participating or plan to participate in any other investigational&#xD;
             device or drug study without prior approval from the Sponsor;&#xD;
&#xD;
          4. Subjects who are known, current alcohol and/or drug abusers&#xD;
&#xD;
          5. Subjects admitted for trauma surgery&#xD;
&#xD;
          6. Subjects with any pre or intra-operative findings identified by the surgeon that may&#xD;
             preclude conduct of the study procedure&#xD;
&#xD;
          7. Subjects that have received a COVID-19 vaccine either 4 weeks prior to surgery or&#xD;
             scheduled to receive COVID-19 vaccine within the 30-day follow-up period&#xD;
&#xD;
          8. Subject with TBS in an actively infected field (Class III Contaminated or Class IV&#xD;
             Dirty or Infected)&#xD;
&#xD;
          9. TBS is from large defects in arteries or veins where the injured vascular wall&#xD;
             requires repair with maintenance of vessel patency and which would result in&#xD;
             persistent exposure of EVARREST to blood flow and pressure during healing and&#xD;
             absorption of the product&#xD;
&#xD;
         10. TBS with major arterial bleeding requiring suture or mechanical ligation;&#xD;
&#xD;
         11. Bleeding site is in, around, or in proximity to foramina in bone, or areas of bony&#xD;
             confine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Days</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Richard Kocharian, M.D., Ph.D.</last_name>
    <phone>1 (908) 642-3787</phone>
    <email>rkochar1@its.jnj.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ellie Barnett</last_name>
    <email>ebarnett@its.jnj.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Alabama Hospital</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35222</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Specialty Care</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>The Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>icahn School of Medicine at Mt Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Univesity of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Birmingham Chrildren's Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Southampton University Hospital</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bleeding, hemostasis, re-bleeding, hemostatic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrin Tissue Adhesive</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Efficacy and safety results related to the primary and secondary endpoints</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/NCT03255174
org study id: BIOS-16-001
nct id: NCT03255174
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to evaluate the safety and hemostatic effectiveness of
      EVARREST as an adjunct to controlling mild to moderate soft hepatic parenchyma or soft tissue
      bleeding during open hepatic, abdominal, pelvic, retroperitoneal, and thoracic (non-cardiac)
      surgery in pediatric population.
This is an open-label, multicenter, single-arm study evaluating the safety and effectiveness
      of EVARREST in controlling mild or moderate bleeding in hepatic parenchyma or soft tissue for
      which standard methods of achieving hemostasis are ineffective or impractical.

      Eligible subjects will be treated with EVARREST. Subjects will be followed post-operatively
      through discharge and at 30 days (+/-14 days) post-surgery.

      Enrollment will be staggered by age. The first group will include 31 subjects ≥1 years to <18
      years of age and the subsequent group will include 4 subjects from 1 month (≥ 28 days from
      birth) to <1 years of age. Ongoing safety assessment will ensure adequate safety monitoring
      occur during the staged enrollment.

      At least thirty-five (35) qualified pediatric subjects with an appropriate mild or moderate
      bleeding TBS will be enrolled in this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Absolute time to hemostasis
time frame: Intraoperative from TBS identification to the last moment in time at which no detectable bleeding at the TBS is observed
description: The absolute time to hemostasis, defined as the absolute time elapsed from TBS identification to the last moment in time at which detectable bleeding at the TBS is observed.
measure: Hemostatic success at 4 minutes
time frame: Intraoperative, 4 minutes after TBS identification
description: Proportion of subjects achieving hemostatic success at 4 minutes following Target Bleeding Site (TBS) identification and no bleeding requiring treatment at the TBS any time prior to final fascial closure.
measure: Hemostatic success at 10 minutes
time frame: Intraoperative, 10 minutes after TBS identification
description: Proportion of subjects achieving hemostatic success at 10 minutes following TBS identification and no bleeding requiring treatment at the TBS any time prior to final fascial closure.
measure: No re-bleeding at the TBS
time frame: Intraoperative, from TBS identification to final fascial closure
description: Proportion of subjects with no re-bleeding at the TBS.
measure: Incidence of adverse events that are potentially related to bleeding at the TBS
time frame: Intraoperative to 30 (+/- 14) days
description: Incidence of adverse events that are potentially related to bleeding at the TBS.
measure: Incidence of adverse events that are potentially related to thrombotic events
time frame: Intraoperative to 30 (+/- 14) days
description: Incidence of adverse events that are potentially related to thrombotic events.
measure: Incidence of re-treatment at the TBS
time frame: Intraoperative, from TBS identification to final fascial closure
measure: Incidence of Adverse Events
time frame: Intraoperative to 30 (+/- 14) days
arm group label: EVARREST® Fibrin Sealant Patch
arm group type: Experimental
description: EVARREST Fibrin Sealant Patch is a sterile, bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.
intervention type: Biological
intervention name: EVARREST® Fibrin Sealant Patch
description: EVARREST Fibrin Sealant Patch is a sterile, bio-absorbable combination product consisting of two constituent parts- a flexible matrix and a coating of biological components (human plasma-derived fibrinogen and thrombin) embedded in a flexible composite patch component.
arm group label: EVARREST® Fibrin Sealant Patch
other name: EVARREST
criteria: 
gender: All
minimum age: 28 Days
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Richard Kocharian, M.D., Ph.D.
phone: 1 (908) 642-3787
email: rkochar1@its.jnj.com
last name: Ellie Barnett
email: ebarnett@its.jnj.com
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hemorrhage
mesh term: Fibrin Tissue Adhesive
sharing ipd: Yes
ipd description: Efficacy and safety results related to the primary and secondary endpoints