<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/NCT04419597</url>
  </required_header>
  <id_info>
    <org_study_id>NEUROHEMOPATCH</org_study_id>
    <nct_id>NCT04419597</nct_id>
  </id_info>
  <brief_title>Hemopatch Safety and Efficacy Evaluation Versus Standard Practice for Sealing the Dura in Cerebrospinal Fluid Leaks</brief_title>
  <official_title>Randomized Multicenter Controlled Study to Evaluate the Safety and Efficacy of HEMOPATCH® Compared to Routine Care for Dural Closure as Reinforcement for the Prevention of Postoperative Cerebrospinal Fluid Leakage (CSF) in Patients Undergoing Posterior Fossa Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Posterior fossa surgeries are generally complicated by difficulties in creating a watertight&#xD;
      dural closure, which often requires the use of dural substitutes. In particular, surgical&#xD;
      procedures at this location are associated with an increased rate of fluid leakage&#xD;
      (cerebrospinal fluid (CSF)) or inflow (blood, air, etc.) creating hydrodynamic complications.&#xD;
      Effective sealing of the dura is required to prevent such complications and infections by&#xD;
      minimizing the introduction of irritating blood products into the CSF. Since true hermetic&#xD;
      dural seals are often impossible to achieve, dural sealants have been developed that can be&#xD;
      applied to the sutured dural perimeter to help prevent complications related to CSF. Adjuvant&#xD;
      use of such sealants may be prudent, particularly in posterior fossa surgeries, as the&#xD;
      incidence of CSF leakage has been reported to be as high as approximately 15-28% with such&#xD;
      surgeries, with an increased risk of leakage. 5.84 times greater than supratentorial&#xD;
      procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Various techniques have been developed to overcome this problem and achieve a tight dural&#xD;
      closure. Although there is published evidence showing the efficacy and safety of some of&#xD;
      these sealants in posterior fossa surgery, the different types of pathologies and various&#xD;
      population risk factors included in these trials make it difficult to interpret the results.&#xD;
      Having selective inclusion criteria and including patients with a selected pathology could be&#xD;
      essential to obtain clearer results.&#xD;
&#xD;
      Postoperative CSF leak has two aspects: one is pseudomeningocele (a subcutaneous collection&#xD;
      of CSF); the other is a CSF fistula in which CSF reaches the skin. This second one is much&#xD;
      more dangerous and constitutes one of the most important complications of this surgery, but&#xD;
      the pseudomeningocele is a clinical demonstration of failure of the dural closure.&#xD;
&#xD;
      HEMOPATCH is a soft, thin, foldable and flexible collagen patch, coated with NHS-PEG.&#xD;
      HEMOPATCH is indicated as a hemostatic device and surgical seal for procedures in which&#xD;
      control of bleeding or leakage of other body fluids or air by conventional surgical&#xD;
      techniques is ineffective or impractical.&#xD;
&#xD;
      Preliminary clinical evidence collects a prospective case series of 200 patients, in which&#xD;
      the authors reviewed the use of HEMOPATCH for dural augmentation in high-risk patients from&#xD;
      2014 to this year. After 2 years of refining the technique, a decrease in CSF leaks from 27%&#xD;
      to 7% was achieved, and no adverse events related to the application of the product were&#xD;
      observed. A retrospective cohort study has recently been published comparing the use of&#xD;
      HEMOPATCH versus routine clinical practice in 290 patients, in which 147 used standard dural&#xD;
      reinforcement techniques, and 143 used HEMOPATCH. The CSF fistula appearance rates were 7.69%&#xD;
      in the HEMOPATCH group, compared to 32.65% in the control group.&#xD;
&#xD;
      These recent results, along with the characteristics and properties of the patch, could make&#xD;
      this sealant a safe and plausible option to achieve sealing after posterior fossa surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 2, 2020</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>N/A</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>proportion of participants with clinically evident CSF leak after the operation up to 4 weeks.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Clinically evident CSF leak, observed from the operation to 4 weeks later. It will be measured every 24 hours until the patient is discharged. The following measurement will be made at the visit of the 4 weeks (+/- 7 days) from the operation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with clinical pseudomeningocele or evident MRI</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical evidence of Pseudomeningocele or by imaging techniques, evaluated by CT or MRI during the 4 postoperative weeks, by MRI at 6 postoperative months, or at any visit of patients within 6 postoperative months according to the criteria of the investigator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with ascent of the cerebellar tonsils</measure>
    <time_frame>6 months</time_frame>
    <description>The elevation of the cerebellar tonsils will be measured, according to the baseline preoperative CT / MRI, in the MRI test performed 6 months after the operation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with readmissions related to CSF leaks</measure>
    <time_frame>4 weeks</time_frame>
    <description>The need for readmission / reoperation related to CSF leak will be collected up to 4 weeks after the operation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Surgical site infections (SSI)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Bacterial or chemical meningitis (SSI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of quality of life (QoL): SF12 questionnaire (Short Form 12 questionnaire)</measure>
    <time_frame>6 months</time_frame>
    <description>The SF-12 measures overall quality of life and includes items that assess participation. The SF-12 is a frequently used measure and has shown to have good internal consistency, reliability, construct validity and responsiveness in patients with chronic (low) back pain (Luo et al., 2003). The measure is a subset of 12 items from the SF-36 including 6 items from the physical summary measure (PCS) and 6 items from the mental summary measure (MCS).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>HEMOPATCH Collagen Patch and PEG Haemostatic Sealant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two units of the large patch are applied as reinforcement of the primary dural seal (HEMOPATCH 4,5x9cm, 1506253).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Usual clinical practice techniques for reinforcing primary dural closure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>HEMOPATCH</intervention_name>
    <description>The treatment will be performed with the HEMOPATCH collagen patch and hemostatic PEG sealant (Baxter), applying two units of the large patch to reinforce the primary dural closure (HEMOPATCH 4.5x9cm, 1506253).</description>
    <arm_group_label>HEMOPATCH Collagen Patch and PEG Haemostatic Sealant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Standard of care</intervention_name>
    <description>Usual clinical practice techniques for reinforcing primary dural closure.</description>
    <arm_group_label>Standard of care treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are planned for non-traumatic posterior fossa surgery&#xD;
&#xD;
          -  Surgery that requires opening and closing of the dura mater.&#xD;
&#xD;
          -  Patients who have a clean surgical wound (class I surgical wound classification)&#xD;
&#xD;
          -  Patients undergoing one of the following surgical procedures:&#xD;
&#xD;
          -  Space occupant injuries (LOEs) rese dried through the following approaches:&#xD;
&#xD;
          -  Approaching the rear pit of the middle line&#xD;
&#xD;
          -  Approach to the posterior paramedian fossa&#xD;
&#xD;
          -  Approach to the cerebellar pontine angle (PC) and the back of the petrous vertex&#xD;
&#xD;
          -  Clinical diagnosis of primary Chiari 1 (CM1) malformation and scheduled decompression&#xD;
             surgery, with evidence of NM of tonsil herniation down by an independent official&#xD;
             radiology report.&#xD;
&#xD;
          -  Subjects who are able to provide written informed consent prior to participating in&#xD;
             the clinical trial.&#xD;
&#xD;
          -  Be over 18 years of age.&#xD;
&#xD;
          -  Understand the purpose of the study and be available for frequent hospital visits.&#xD;
&#xD;
          -  Women of childbearing potential and males with partners of childbearing potential&#xD;
             should commit to using a highly effective method of contraception (such as surgical&#xD;
             sterilization, double barrier method, oral contraceptives or contraceptive hormonal&#xD;
             implants) and to continue to use them for up to 6 months after surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing a supratentorial surgical procedure/approach.&#xD;
&#xD;
          -  Patients undergoing any other approach/surgical procedure at the base of the skull&#xD;
             that is not in the posterior pit:&#xD;
&#xD;
          -  Side boarding of the foramen magno: far side, extreme side, anterolateral,&#xD;
             posterolateral,&#xD;
&#xD;
          -  Approaching the jugular foramen: infratemporal, condylar juxta, transjugular&#xD;
&#xD;
          -  Approach to the middle pit: subtemporal (+/-petrous apex perforation), pterional&#xD;
             approach (any temporary fronto approach +/- orbitozygomatic replacement)&#xD;
&#xD;
          -  Approach to the previous pit: subfrontal (uni or bilateral)&#xD;
&#xD;
          -  Presence of hydrocephalus not resolved prior to surgery&#xD;
&#xD;
          -  Previous surgery in the posterior pit.&#xD;
&#xD;
          -  Pre-radiation therapy treatment.&#xD;
&#xD;
          -  Previous (within the last 6 months) or anticipated neurosurgical procedure involving&#xD;
             the opening of the dura mater that may affect the safety assessment&#xD;
&#xD;
          -  &gt; 1 dural opening&#xD;
&#xD;
          -  Inability to understand informed consent or unwillingness to participate in the study.&#xD;
&#xD;
          -  Inability, at the time of consent, to return for follow-up evaluations after surgery&#xD;
&#xD;
          -  Evidence of spinal dysraphism.&#xD;
&#xD;
          -  Allergy, hypersensitivity or history of allergic reaction to Hemopatch or its&#xD;
             components (to bovine proteins or bright blue dye: FD&amp;C blue No. 1 [blue 1]).&#xD;
&#xD;
          -  Evidence of an infection within 5 days prior to the start of the study.&#xD;
&#xD;
          -  Pregnancy or planning to become pregnant during the course of the study. Breast&#xD;
             feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Posterior fossa</keyword>
  <keyword>HEMOPATCH</keyword>
  <keyword>cerebrospinal fluid (CSF)</keyword>
  <keyword>CSF leak</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04419597
org study id: NEUROHEMOPATCH
nct id: NCT04419597
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Posterior fossa surgeries are generally complicated by difficulties in creating a watertight
      dural closure, which often requires the use of dural substitutes. In particular, surgical
      procedures at this location are associated with an increased rate of fluid leakage
      (cerebrospinal fluid (CSF)) or inflow (blood, air, etc.) creating hydrodynamic complications.
      Effective sealing of the dura is required to prevent such complications and infections by
      minimizing the introduction of irritating blood products into the CSF. Since true hermetic
      dural seals are often impossible to achieve, dural sealants have been developed that can be
      applied to the sutured dural perimeter to help prevent complications related to CSF. Adjuvant
      use of such sealants may be prudent, particularly in posterior fossa surgeries, as the
      incidence of CSF leakage has been reported to be as high as approximately 15-28% with such
      surgeries, with an increased risk of leakage. 5.84 times greater than supratentorial
      procedures.
Various techniques have been developed to overcome this problem and achieve a tight dural
      closure. Although there is published evidence showing the efficacy and safety of some of
      these sealants in posterior fossa surgery, the different types of pathologies and various
      population risk factors included in these trials make it difficult to interpret the results.
      Having selective inclusion criteria and including patients with a selected pathology could be
      essential to obtain clearer results.

      Postoperative CSF leak has two aspects: one is pseudomeningocele (a subcutaneous collection
      of CSF); the other is a CSF fistula in which CSF reaches the skin. This second one is much
      more dangerous and constitutes one of the most important complications of this surgery, but
      the pseudomeningocele is a clinical demonstration of failure of the dural closure.

      HEMOPATCH is a soft, thin, foldable and flexible collagen patch, coated with NHS-PEG.
      HEMOPATCH is indicated as a hemostatic device and surgical seal for procedures in which
      control of bleeding or leakage of other body fluids or air by conventional surgical
      techniques is ineffective or impractical.

      Preliminary clinical evidence collects a prospective case series of 200 patients, in which
      the authors reviewed the use of HEMOPATCH for dural augmentation in high-risk patients from
      2014 to this year. After 2 years of refining the technique, a decrease in CSF leaks from 27%
      to 7% was achieved, and no adverse events related to the application of the product were
      observed. A retrospective cohort study has recently been published comparing the use of
      HEMOPATCH versus routine clinical practice in 290 patients, in which 147 used standard dural
      reinforcement techniques, and 143 used HEMOPATCH. The CSF fistula appearance rates were 7.69%
      in the HEMOPATCH group, compared to 32.65% in the control group.

      These recent results, along with the characteristics and properties of the patch, could make
      this sealant a safe and plausible option to achieve sealing after posterior fossa surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: proportion of participants with clinically evident CSF leak after the operation up to 4 weeks.
time frame: 4 weeks
description: Clinically evident CSF leak, observed from the operation to 4 weeks later. It will be measured every 24 hours until the patient is discharged. The following measurement will be made at the visit of the 4 weeks (+/- 7 days) from the operation
measure: Proportion of participants with clinical pseudomeningocele or evident MRI
time frame: 6 months
description: Clinical evidence of Pseudomeningocele or by imaging techniques, evaluated by CT or MRI during the 4 postoperative weeks, by MRI at 6 postoperative months, or at any visit of patients within 6 postoperative months according to the criteria of the investigator
measure: Proportion of participants with ascent of the cerebellar tonsils
time frame: 6 months
description: The elevation of the cerebellar tonsils will be measured, according to the baseline preoperative CT / MRI, in the MRI test performed 6 months after the operation.
measure: Proportion of participants with readmissions related to CSF leaks
time frame: 4 weeks
description: The need for readmission / reoperation related to CSF leak will be collected up to 4 weeks after the operation.
measure: Number of Participants with Surgical site infections (SSI)
time frame: 4 weeks
description: Bacterial or chemical meningitis (SSI)
measure: Assessment of quality of life (QoL): SF12 questionnaire (Short Form 12 questionnaire)
time frame: 6 months
description: The SF-12 measures overall quality of life and includes items that assess participation. The SF-12 is a frequently used measure and has shown to have good internal consistency, reliability, construct validity and responsiveness in patients with chronic (low) back pain (Luo et al., 2003). The measure is a subset of 12 items from the SF-36 including 6 items from the physical summary measure (PCS) and 6 items from the mental summary measure (MCS).
arm group label: HEMOPATCH Collagen Patch and PEG Haemostatic Sealant
arm group type: Experimental
description: Two units of the large patch are applied as reinforcement of the primary dural seal (HEMOPATCH 4,5x9cm, 1506253).
arm group label: Standard of care treatment
arm group type: Active Comparator
description: Usual clinical practice techniques for reinforcing primary dural closure.
intervention type: Device
intervention name: HEMOPATCH
description: The treatment will be performed with the HEMOPATCH collagen patch and hemostatic PEG sealant (Baxter), applying two units of the large patch to reinforce the primary dural closure (HEMOPATCH 4.5x9cm, 1506253).
arm group label: HEMOPATCH Collagen Patch and PEG Haemostatic Sealant
intervention type: Device
intervention name: Standard of care
description: Usual clinical practice techniques for reinforcing primary dural closure.
arm group label: Standard of care treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Spain
responsible party type: Sponsor
sharing ipd: No