<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/NCT02220621</url>
  </required_header>
  <id_info>
    <org_study_id>FNL-2011-03</org_study_id>
    <nct_id>NCT02220621</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Crosslinked Hyaluronan Gel for Preventing Intrauterine Adhesion</brief_title>
  <official_title>A Prospective, Multi-center, Randomized, Controlled Clinical Study on Self-crosslinked Sodium Hyaluronate Gel for Prevention of Intrauterine Adhesion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xiaozheng Shu</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioRegen Biomedical (CHangzhou) Co., Ltd</source>
  <brief_summary>
    <textblock>
      Intrauterine adhesion (IUA) is the adhesion of intrauterine tissues due to the exposure of&#xD;
      myometrial tissues caused by the endometrial basal injury. IUA is clinically manifested as&#xD;
      symptoms such as abdominal pain, hypomenorrhea or amenorrhea, sterility and habitual&#xD;
      abortion, which seriously affect the patients quality of life.&#xD;
&#xD;
      Preventing IUA has been tried using different methods such as barrier or stent in order to&#xD;
      separate the opposing endometrium during the tissue healing processes. Although some&#xD;
      successes have been reported there are still some challenges need to be dealt with.&#xD;
&#xD;
      One of the barrier materials for preventing IUA is made of hyaluronic acid (HA). HA is a&#xD;
      natural ECM of human tissue with excellent biocompatibility and promotes the scar-free wound&#xD;
      repair. The self-crosslinked esterified HA gel has demonstrated the capacity to prevent IUA&#xD;
      in clinical studies.&#xD;
&#xD;
      A novel self-crosslinked HA gel is developed by BioRegen Biomedical（Changzhou）Co., Ltd with&#xD;
      proprietary technologies. This product is a highly viscoelastic crosslinked gel that&#xD;
      overcomes the shortcoming of sodium hyaluronate with high motility and too quick degradation&#xD;
      in vivo. For this product, the results of animal experiments and various safety features have&#xD;
      been designed and tested conforming to the national regulations and standards. In order to&#xD;
      launch this product to the market, this prospective, randomized and controlled clinical trial&#xD;
      is designed and will be performed to verify its safety/efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <primary_completion_date type="Actual">April 2012</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>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the percentage of patients free from IUA</measure>
    <time_frame>3 months after surgery</time_frame>
    <description>Second look hysteroscopic examinations were performed at 3 months postoperatively. The adhesion was scored at adhesiolysis surgery and at follow-up hysteroscopy according to American Fertility Society scoring system.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effective rate</measure>
    <time_frame>three months after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total AFS score</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The score for each subcategory of AFS scoring system</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The safety</measure>
    <time_frame>3 months</time_frame>
    <description>Evaluated based on the number of patients shown complications and incidence rate for severe adverse events</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety</measure>
    <time_frame>3 months</time_frame>
    <description>Severe adverse event (SAE): cause prolonged hospitalization and disability to the patient.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Intrauterine Adhesion</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After the hysteroscopic adhesiolysis, crosslinked hyaluronic acid gel is applied into the uterine cavity, then a Foleys balloon catheter is inserted into the uterine cavity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After hysteroscopic adhesiolysis, a Foleys balloon catheter is inserted into the unterine cavity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Crosslinked hyaluronic acid gel</intervention_name>
    <description>After hysteroscopic adhesiolysis, MateRegen Gel IU is applied into the uterine cavity together with a Foley balloon catheter.</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>MateRegen Gel IU.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Foleys balloon catheter</intervention_name>
    <description>After adhesivolysis, the Foleys balloon catheter is inserted into the uterine cavityand expanded with normal saline.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patients who are 20-40 years old who is diagnosed as intrauterine adhesion, and&#xD;
             did not receive adhesiolysis surgery.&#xD;
&#xD;
          -  Patients who signed the informed consent form (ICF) and agreed to take contraceptive&#xD;
             measures within 3 months after the surgery.&#xD;
&#xD;
          -  Physical examination and routine laboratory tests demonstrated no systemic diseases.&#xD;
&#xD;
          -  According to the AFS scoring system on the IUA (1988) only those patients with&#xD;
             moderate to severe IUA (i.e. total AFS score larger than 4 points) were enrolled in&#xD;
             this clinical trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who is allergic to hyaluronan or its derivatives.&#xD;
&#xD;
          -  Patients with inflammation of reproductive organs, pelvic cavity inflammation,&#xD;
             malignant tumor of reproductive organs and other systemic diseases that could cause&#xD;
             metrorrhagia.&#xD;
&#xD;
          -  Patients with malformation of reproductive organs.&#xD;
&#xD;
          -  Patients who may not take effective contraceptive measures within 3 months after the&#xD;
             surgery. Patients who were suffering severe systemic diseases such as coagulative&#xD;
             disorders, cardiovascular diseases and long-term alcoholism and drug abuse were also&#xD;
             excluded from this clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Third Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The People's Hospital of Hunan Province</name>
      <address>
        <city>Changshu</city>
        <state>Hunan</state>
        <zip>410005</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The People's Hospital of Chenzhou City,</name>
      <address>
        <city>Chenzhou</city>
        <state>Hunan</state>
        <zip>423000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, Cirillo D, Taylor A, Nappi C. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod. 2003 Sep;18(9):1918-21. doi: 10.1093/humrep/deg368.</citation>
    <PMID>12923149</PMID>
  </reference>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 18, 2014</last_update_submitted>
  <last_update_submitted_qc>August 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>BioRegen Biomedical (CHangzhou) Co., Ltd</investigator_affiliation>
    <investigator_full_name>Xiaozheng Shu</investigator_full_name>
    <investigator_title>CEO</investigator_title>
  </responsible_party>
  <keyword>Intrauterine adhesion</keyword>
  <keyword>crosslinked hyaluronan gel</keyword>
  <keyword>hysteroscopy</keyword>
  <keyword>clinical trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tissue Adhesions</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02220621
org study id: FNL-2011-03
nct id: NCT02220621
lead sponsor: 
Intrauterine adhesion (IUA) is the adhesion of intrauterine tissues due to the exposure of
      myometrial tissues caused by the endometrial basal injury. IUA is clinically manifested as
      symptoms such as abdominal pain, hypomenorrhea or amenorrhea, sterility and habitual
      abortion, which seriously affect the patients quality of life.

      Preventing IUA has been tried using different methods such as barrier or stent in order to
      separate the opposing endometrium during the tissue healing processes. Although some
      successes have been reported there are still some challenges need to be dealt with.

      One of the barrier materials for preventing IUA is made of hyaluronic acid (HA). HA is a
      natural ECM of human tissue with excellent biocompatibility and promotes the scar-free wound
      repair. The self-crosslinked esterified HA gel has demonstrated the capacity to prevent IUA
      in clinical studies.

      A novel self-crosslinked HA gel is developed by BioRegen Biomedical（Changzhou）Co., Ltd with
      proprietary technologies. This product is a highly viscoelastic crosslinked gel that
      overcomes the shortcoming of sodium hyaluronate with high motility and too quick degradation
      in vivo. For this product, the results of animal experiments and various safety features have
      been designed and tested conforming to the national regulations and standards. In order to
      launch this product to the market, this prospective, randomized and controlled clinical trial
      is designed and will be performed to verify its safety/efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: the percentage of patients free from IUA
time frame: 3 months after surgery
description: Second look hysteroscopic examinations were performed at 3 months postoperatively. The adhesion was scored at adhesiolysis surgery and at follow-up hysteroscopy according to American Fertility Society scoring system.
measure: Effective rate
time frame: three months after surgery
measure: Total AFS score
time frame: 3 months
measure: The score for each subcategory of AFS scoring system
time frame: 3 months
measure: The safety
time frame: 3 months
description: Evaluated based on the number of patients shown complications and incidence rate for severe adverse events
measure: Safety
time frame: 3 months
description: Severe adverse event (SAE): cause prolonged hospitalization and disability to the patient.
arm group label: Treatment
arm group type: Experimental
description: After the hysteroscopic adhesiolysis, crosslinked hyaluronic acid gel is applied into the uterine cavity, then a Foleys balloon catheter is inserted into the uterine cavity.
arm group label: Control
arm group type: Active Comparator
description: After hysteroscopic adhesiolysis, a Foleys balloon catheter is inserted into the unterine cavity.
intervention type: Device
intervention name: Crosslinked hyaluronic acid gel
description: After hysteroscopic adhesiolysis, MateRegen Gel IU is applied into the uterine cavity together with a Foley balloon catheter.
arm group label: Treatment
other name: MateRegen Gel IU.
intervention type: Device
intervention name: Foleys balloon catheter
description: After adhesivolysis, the Foleys balloon catheter is inserted into the uterine cavityand expanded with normal saline.
arm group label: Control
arm group label: Treatment
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: No
facility: 
facility: 
facility: 
country: China
citation: Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, Cirillo D, Taylor A, Nappi C. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod. 2003 Sep;18(9):1918-21. doi: 10.1093/humrep/deg368.
PMID: 12923149
responsible party type: Sponsor-Investigator
investigator affiliation: BioRegen Biomedical (CHangzhou) Co., Ltd
investigator full name: Xiaozheng Shu
investigator title: CEO
mesh term: Tissue Adhesions
mesh term: Hyaluronic Acid