<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/NCT04498026</url>
  </required_header>
  <id_info>
    <org_study_id>HBMT-US-2019-001</org_study_id>
    <nct_id>NCT04498026</nct_id>
  </id_info>
  <brief_title>Adherus™ Dural Sealant in Spinal Procedures</brief_title>
  <official_title>A Pivotal Clinical Trial Evaluating the Safety and Effectiveness of Adherus™ AutoSpray and Adherus™ AutoSpray ET Dural Sealant When Used as a Dural Sealant in Spinal Procedures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stryker Craniomaxillofacial</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Laboratory Corporation of America</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stryker Craniomaxillofacial</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test an experimental device, the Adherus AutoSpray and&#xD;
      Adherus AutoSpray ET Dural Sealant, in spinal surgical procedures.&#xD;
&#xD;
      This study is being done to compare Adherus AutoSpray and Adherus AutoSpray ET Dural Sealant&#xD;
      to DuraSeal Exact Spinal Sealant, which has already received Federal Food and Drug&#xD;
      Administration (FDA) approval in spinal procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, randomized, controlled, single-blind, multicenter, pivotal trial that&#xD;
      will evaluate the safety and effectiveness of Adherus Dural Sealant when used in conjunction&#xD;
      with standard methods of dural repair in spinal procedures. This trial uses the commercially&#xD;
      available DuraSeal Exact as an active control. The trial is designed to demonstrate&#xD;
      non-inferiority of Adherus Dural Sealant to DuraSeal Exact.&#xD;
&#xD;
      Subjects who are undergoing spinal surgery, consent to participate in this trial and&#xD;
      experience a durotomy will be considered for study enrollment. Following a two-tiered&#xD;
      inclusion/exclusion consideration, subjects will be randomized intraoperatively using a 1:1&#xD;
      randomization ratio. Up to 114 subjects will be randomized to treatment with either Adherus&#xD;
      Dural Sealant or DuraSeal Exact with at least 50% of subjects undergoing procedures at lumbar&#xD;
      or lumbosacral levels. Up to 30 investigational sites within the United States will&#xD;
      participate in this trial.&#xD;
&#xD;
      A primary composite endpoint evaluating safety and effectiveness will be measured within a&#xD;
      90-day required follow-up period post-procedure. Subjects will be followed at discharge or&#xD;
      between postoperative days (POD) 1-4 from the index procedure (whichever occurs first) and at&#xD;
      30 days and 90 days post-index procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">November 19, 2020</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>Phase 3</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of treated subjects who are free from the following incidences:</measure>
    <time_frame>90 Days</time_frame>
    <description>CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 90-day follow-up period following the index procedure&#xD;
Unplanned retreatment of the original surgical site adjudicated by the Clinical Events Committee (CEC) to be device-related, other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 90-day follow-up period including:&#xD;
treatment for deep infection&#xD;
treatment for meningitis&#xD;
minimally invasive procedures or return to the operating room for neurosurgical complications</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoints, which will only be tested for superiority of Adherus over DuraSeal Exact after the primary objective of the study has been met:</measure>
    <time_frame>30 Day, 90 Day</time_frame>
    <description>CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 30-day and 90-day follow-up period following the index procedure&#xD;
Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 30-day and 90-day follow-up period including:&#xD;
treatment for deep infection&#xD;
treatment for meningitis&#xD;
minimally invasive procedures or return to the operating room for neurosurgical complications</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">114</enrollment>
  <condition>Spinal Duraplasty</condition>
  <arm_group>
    <arm_group_label>Adherus Dural Sealant System</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Device: Adherus Dural Sealant, In situ polymerizing sealant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DuraSeal Exact Dural Sealant System</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Device: DuraSeal Exact (P080013b)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Adherus Dural Sealant System</intervention_name>
    <description>Adherus Dural Sealant, In situ polymerizing sealant</description>
    <arm_group_label>Adherus Dural Sealant System</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>DuraSeal Exact Dural Sealant System</intervention_name>
    <description>DuraSeal Exact (P080013b)</description>
    <arm_group_label>DuraSeal Exact Dural Sealant System</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is ≥ 18 and ≤ 75 years old.&#xD;
&#xD;
          2. Subject is scheduled for an elective spinal procedure that will require a planned&#xD;
             durotomy.&#xD;
&#xD;
          3. Subject requires a procedure involving a Class I/clean wound (uninfected surgical&#xD;
             wound in which no inflammation is encountered).&#xD;
&#xD;
          4. Subject is able and willing to provide informed consent and HIPAA authorization.&#xD;
&#xD;
          5. Subject is able and willing to meet all study requirements, including attending all&#xD;
             post-index procedure assessment visits and radiological tests.&#xD;
&#xD;
             Intra-Operative Inclusion Criteria:&#xD;
&#xD;
          6. Subject has durotomy edges that can be re-approximated using the investigator's&#xD;
             standard methods of dural repair.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has clinically significant hydrocephalus or clinical evidence of altered CSF&#xD;
             dynamics.&#xD;
&#xD;
          2. Subject has a pre-existing external lumbar CSF drain or internal CSF shunt.&#xD;
&#xD;
          3. Subject has experienced previous CSF leak (secondary to trauma, neoplasm, surgery, or&#xD;
             other etiology).&#xD;
&#xD;
          4. Subject is undergoing a Chiari malformation procedure.&#xD;
&#xD;
          5. Subject has undergone a previous spinal procedure in the same anatomical location.&#xD;
&#xD;
          6. Subject has had radiation treatment to the surgical site, or standard fractionated&#xD;
             radiation therapy is planned within ten days post indexprocedure.&#xD;
&#xD;
          7. Subject has spinal metallic implants that may cause significant imaging artifact on&#xD;
             the MRI evaluation of the spine.&#xD;
&#xD;
          8. Subject has metallic implant(s) that are not MRI compatible, e.g., cochlear implant,&#xD;
             neurostimulator, stent, surgical clip, cardiac pacemakers, or other non-MRI compatible&#xD;
             implants, or an elective implant of such devices is planned during the course of the&#xD;
             study. Note: mercury amalgam dental fillings or similar metallic dental prostheses are&#xD;
             not an exclusion criterion.&#xD;
&#xD;
          9. Subject has a known malignancy or another condition with anticipated survival shorter&#xD;
             than six months.&#xD;
&#xD;
         10. Subject has undergone chemotherapy treatment, excluding hormonal therapy, within three&#xD;
             weeks prior to the planned index procedure, or chemotherapy treatment is planned&#xD;
             within two weeks after the index procedure is performed.&#xD;
&#xD;
         11. Subject has been treated with chronic steroid therapy (defined as regular (daily)&#xD;
             administration of steroid agent(s) for ≥ 8 weeks) unless discontinued greater than&#xD;
             four weeks prior to the planned index procedure. Note: standard acute perioperative&#xD;
             steroids are permitted; administration of steroid agents for &lt; 8 weeks duration prior&#xD;
             to the planned index procedure is permitted.&#xD;
&#xD;
         12. Subject has received warfarin, heparin, other anticoagulant agents, aspirin or non&#xD;
             steroid anti-inflammatory agents on a daily basis and pre-surgical, standard of care&#xD;
             drug wash-out did not occur.&#xD;
&#xD;
         13. Subject has a compromised immune system or autoimmune disease or is on chronic&#xD;
             immunosuppressant agents at baseline.&#xD;
&#xD;
         14. Subject has a systemic infection or evidence of any infection near planned operative&#xD;
             site.&#xD;
&#xD;
         15. Subject has a serum creatinine level &gt; 2.0 mg/dL.&#xD;
&#xD;
         16. Subject has a serum total bilirubin &gt; 2.5 mg/dL at baseline.&#xD;
&#xD;
         17. Subject has uncontrolled diabetes as evidenced by an HbA1c &gt; 7% prior to surgery.&#xD;
&#xD;
         18. Subject has a known allergy to FD&amp;C Blue #1 and/or FD&amp;C Yellow #5 or any of the&#xD;
             constituents of the dural sealants.&#xD;
&#xD;
         19. Subject is pregnant, breast-feeding, or intends to become pregnant during the course&#xD;
             of the study.&#xD;
&#xD;
         20. Subject is participating in a clinical trial of another investigational drug or device&#xD;
             and has not completed the required follow-up period.&#xD;
&#xD;
             Intra-Operative Exclusion Criteria:&#xD;
&#xD;
         21. Subject has an incidental finding that meets any pre-operative exclusion criterion&#xD;
             listed above.&#xD;
&#xD;
         22. Subject's dural defect cannot be closed with suture and/or duraplasty material.&#xD;
&#xD;
         23. Subject has a gap &gt; 2 mm present between dural edges, or between the edge of dura and&#xD;
             duraplasty material, based on visual estimate by surgeon before application of the&#xD;
             surgical sealant.&#xD;
&#xD;
         24. Subject had undergone laminoplasty decompression.&#xD;
&#xD;
         25. Subject had undergone a syringomyelia procedure where the shunt is not placed in the&#xD;
             subarachnoid position.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Health</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic (FL)</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Steward St. Elizabeth's Medical Center</name>
      <address>
        <city>Brighton</city>
        <state>Massachusetts</state>
        <zip>02135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Neurosurgery &amp; Spine Associates</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Research Institute</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas M.D. Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Clinic</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>August 3, 2023</last_update_submitted>
  <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adherus Dural Sealant</keyword>
  <keyword>Adherus AutoSpray Dural Sealant</keyword>
  <keyword>Dura mater</keyword>
  <keyword>Durotomy</keyword>
  <keyword>CSF leak</keyword>
  <!-- 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/NCT04498026
org study id: HBMT-US-2019-001
nct id: NCT04498026
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The purpose of this study is to test an experimental device, the Adherus AutoSpray and
      Adherus AutoSpray ET Dural Sealant, in spinal surgical procedures.

      This study is being done to compare Adherus AutoSpray and Adherus AutoSpray ET Dural Sealant
      to DuraSeal Exact Spinal Sealant, which has already received Federal Food and Drug
      Administration (FDA) approval in spinal procedures.
This is a prospective, randomized, controlled, single-blind, multicenter, pivotal trial that
      will evaluate the safety and effectiveness of Adherus Dural Sealant when used in conjunction
      with standard methods of dural repair in spinal procedures. This trial uses the commercially
      available DuraSeal Exact as an active control. The trial is designed to demonstrate
      non-inferiority of Adherus Dural Sealant to DuraSeal Exact.

      Subjects who are undergoing spinal surgery, consent to participate in this trial and
      experience a durotomy will be considered for study enrollment. Following a two-tiered
      inclusion/exclusion consideration, subjects will be randomized intraoperatively using a 1:1
      randomization ratio. Up to 114 subjects will be randomized to treatment with either Adherus
      Dural Sealant or DuraSeal Exact with at least 50% of subjects undergoing procedures at lumbar
      or lumbosacral levels. Up to 30 investigational sites within the United States will
      participate in this trial.

      A primary composite endpoint evaluating safety and effectiveness will be measured within a
      90-day required follow-up period post-procedure. Subjects will be followed at discharge or
      between postoperative days (POD) 1-4 from the index procedure (whichever occurs first) and at
      30 days and 90 days post-index procedure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: The proportion of treated subjects who are free from the following incidences:
time frame: 90 Days
description: CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 90-day follow-up period following the index procedure
Unplanned retreatment of the original surgical site adjudicated by the Clinical Events Committee (CEC) to be device-related, other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 90-day follow-up period including:
treatment for deep infection
treatment for meningitis
minimally invasive procedures or return to the operating room for neurosurgical complications
measure: Secondary endpoints, which will only be tested for superiority of Adherus over DuraSeal Exact after the primary objective of the study has been met:
time frame: 30 Day, 90 Day
description: CSF leak or pseudomeningocele diagnosed by physical examination, biochemical assay or imaging study during the 30-day and 90-day follow-up period following the index procedure
Unplanned retreatment of the original surgical site adjudicated by the CEC to be device-related, other than CSF leak or pseudomeningocele formation or those related to the subject's pre-existing condition, during the 30-day and 90-day follow-up period including:
treatment for deep infection
treatment for meningitis
minimally invasive procedures or return to the operating room for neurosurgical complications
arm group label: Adherus Dural Sealant System
arm group type: Experimental
description: Device: Adherus Dural Sealant, In situ polymerizing sealant
arm group label: DuraSeal Exact Dural Sealant System
arm group type: Active Comparator
description: Device: DuraSeal Exact (P080013b)
intervention type: Device
intervention name: Adherus Dural Sealant System
description: Adherus Dural Sealant, In situ polymerizing sealant
arm group label: Adherus Dural Sealant System
intervention type: Device
intervention name: DuraSeal Exact Dural Sealant System
description: DuraSeal Exact (P080013b)
arm group label: DuraSeal Exact Dural Sealant System
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
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country: United States
responsible party type: Sponsor