<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/NCT04498260</url>
  </required_header>
  <id_info>
    <org_study_id>NP888/2016</org_study_id>
    <nct_id>NCT04498260</nct_id>
  </id_info>
  <brief_title>Intralesional Steroid Injection Versus Oral Prednisolone in Prevention of Esophageal Stricture</brief_title>
  <official_title>Prospective, Randomized Trial of Intralesional Steroid Injection Versus Oral Prednisolone in Prevention of Esophageal Stricture After Endoscopic Submucosal Dissection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto do Cancer do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto do Cancer do Estado de São Paulo</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Endoscopic resection of superficial esophageal neoplasms is already a reality and presents&#xD;
      important advantages when compared to esophagectomy as fewer complications and better quality&#xD;
      of life. However, extensive resections can lead to difficult-to-manage stenoses. There are&#xD;
      several therapies available in order to prevent this stenosis but, to date, there is no&#xD;
      definition of the gold standard.&#xD;
&#xD;
      The objective of this study was to compare the use of intralesional steroid injection versus&#xD;
      oral prednisolone after endoscopic submucosal dissection and to evaluate the stenosis rate,&#xD;
      number of dilations to resolve the stenosis and complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endoscopic resection of superficial esophageal neoplasms is widely used as an alternative to&#xD;
      esophagectomy, since it is less invasive, besides presenting good clinical results. Compared&#xD;
      with esophagectomy, patients submitted to endoscopic resection present shorter&#xD;
      hospitalization time, lower incidence of complications and better quality of life in the long&#xD;
      term.&#xD;
&#xD;
      However, repair of esophageal ulcer, caused by endoscopic resection, which occupies three&#xD;
      quarters or more of the circumference of the organ, can result in the formation of stenosis.&#xD;
&#xD;
      In the past, there was no consensus on the use of preventive therapies for esophageal&#xD;
      stenosis after extensive ESD. However, Oliveira et al recently demonstrated through&#xD;
      systematic review and meta-analysis that the use of these therapies reduces the rate of&#xD;
      stenosis (40% on average), decreased the number of dilations to resolve the stenosis (8&#xD;
      sessions less ), Without altering the number of complications.&#xD;
&#xD;
      Theoretically, corticosteroids are the most appropriate choice due to their mechanism of&#xD;
      action, modulating wound healing by preventing inflammation, by reducing prolyl hydroxylase,&#xD;
      which helps reduce collagen production.&#xD;
&#xD;
      However, treatment with corticosteroids, especially at high oral doses, can cause several&#xD;
      adverse effects, such as immunosuppression, diabetes, psychiatric disorders, osteoporosis,&#xD;
      optic lesion and peptic ulcer. Thus, the use of local corticosteroid injection could minimize&#xD;
      these side effects. However, local injection implies risks of bleeding and perforation, and&#xD;
      is of limited use in patients receiving anticoagulant or antiplatelet therapy.&#xD;
&#xD;
      The objective of this study was to compare the local corticosteroid injection and the use of&#xD;
      oral corticosteroids to prevent stenosis after extensive submucosal endoscopic resection of&#xD;
      superficial esophageal carcinoma, in relation to the stenosis rate, number of dilations&#xD;
      necessary to resolve the stenosis and frequency of complications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Anticipated">June 21, 2021</completion_date>
  <primary_completion_date type="Anticipated">March 21, 2021</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>Early Stenosis rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Stenosis to the passage of the standard endoscopic (9.8 mm)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Late Stenosis rate</measure>
    <time_frame>24 weeks</time_frame>
    <description>Stenosis to the passage of the standard endoscopic (9.8 mm)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Early resistance rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Resistance to the passage of the standard endoscopic (9.8 mm)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Late resistance rate</measure>
    <time_frame>24 weeks</time_frame>
    <description>Resistance to the passage of the standard endoscopic (9.8 mm)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of dilations to solve the stenosis</measure>
    <time_frame>24 weeks</time_frame>
    <description>Number of endoscopic dilations (Savary or balloon)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Complications</measure>
    <time_frame>24 weeks</time_frame>
    <description>Complications related to the procedure and preventive therapy.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Esophageal Stenosis</condition>
  <arm_group>
    <arm_group_label>Local steroid-triamcinolone acetonide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Local steroid (triamcinolone acetonide) injection to the ulcer immediately after ESD. Total amount of injected triamcinolone is 100 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral steroid-predonisolone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(predonisolone) administration three days after ESD. Predonisolone is administered over 8 weeks, started at 30 mg/day and tapered 30, 30, 25, 25, 20, 15, 10 and 5 every 7 days, totaling 8 weeks of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Local steroid - triamcinolone acetonide</intervention_name>
    <description>(triamcinolone acetonide)</description>
    <arm_group_label>Local steroid-triamcinolone acetonide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral steroid - predonisolone</intervention_name>
    <description>(predonisolone)</description>
    <arm_group_label>Oral steroid-predonisolone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of superficial esophageal neoplasm submitted to submucosal&#xD;
             endoscopic resection greater than 3/4 of the organ circumference;&#xD;
&#xD;
          -  Absence of lymph node or distant metastases, evaluated through echoendoscopy, CT and&#xD;
             PET-CT;&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of invasive esophageal neoplasia&#xD;
&#xD;
          -  Hepatical cirrhosis&#xD;
&#xD;
          -  Diabetes mellitus with fasting glycemia above 200mg%&#xD;
&#xD;
          -  Use of corticosteroids in the 30 days prior to ESD&#xD;
&#xD;
          -  INR&gt; 1.5&#xD;
&#xD;
          -  Platelet count less than 50,000&#xD;
&#xD;
          -  Active gastrointestinal ulcer&#xD;
&#xD;
          -  Severe psychiatric illness&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  History of allergy or hypersensitivity to corticosteroids or proton pump inhibitor&#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_contact>
    <last_name>Fauze Maluf-Filho, PhD</last_name>
    <phone>55 11 99191-9014</phone>
    <email>fauze.maluf@terra.com.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joel F Oliveira, MD</last_name>
    <phone>55 11 96382-0289</phone>
    <email>jfoliveira1@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto do Câncer do Estado de São Paulo - ICESP</name>
      <address>
        <city>São Paulo</city>
        <zip>01246-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fauze Fauze-Maluf, MD, PHD</last_name>
      <phone>5511991919014</phone>
      <email>fauze.maluf@terra.com.br</email>
    </contact>
    <investigator>
      <last_name>Fauze Maluf-FIlho, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 30, 2019</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>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>endoscopy submucosal dissection</keyword>
  <keyword>ESD</keyword>
  <keyword>esophageal stenosis</keyword>
  <keyword>esophageal stricture</keyword>
  <keyword>steroid injection</keyword>
  <keyword>oral prednisolone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Stenosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triamcinolone</mesh_term>
    <mesh_term>Triamcinolone Acetonide</mesh_term>
    <mesh_term>Triamcinolone hexacetonide</mesh_term>
    <mesh_term>Triamcinolone diacetate</mesh_term>
  </intervention_browse>
  <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/NCT04498260
org study id: NP888/2016
nct id: NCT04498260
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Endoscopic resection of superficial esophageal neoplasms is already a reality and presents
      important advantages when compared to esophagectomy as fewer complications and better quality
      of life. However, extensive resections can lead to difficult-to-manage stenoses. There are
      several therapies available in order to prevent this stenosis but, to date, there is no
      definition of the gold standard.

      The objective of this study was to compare the use of intralesional steroid injection versus
      oral prednisolone after endoscopic submucosal dissection and to evaluate the stenosis rate,
      number of dilations to resolve the stenosis and complications.
Endoscopic resection of superficial esophageal neoplasms is widely used as an alternative to
      esophagectomy, since it is less invasive, besides presenting good clinical results. Compared
      with esophagectomy, patients submitted to endoscopic resection present shorter
      hospitalization time, lower incidence of complications and better quality of life in the long
      term.

      However, repair of esophageal ulcer, caused by endoscopic resection, which occupies three
      quarters or more of the circumference of the organ, can result in the formation of stenosis.

      In the past, there was no consensus on the use of preventive therapies for esophageal
      stenosis after extensive ESD. However, Oliveira et al recently demonstrated through
      systematic review and meta-analysis that the use of these therapies reduces the rate of
      stenosis (40% on average), decreased the number of dilations to resolve the stenosis (8
      sessions less ), Without altering the number of complications.

      Theoretically, corticosteroids are the most appropriate choice due to their mechanism of
      action, modulating wound healing by preventing inflammation, by reducing prolyl hydroxylase,
      which helps reduce collagen production.

      However, treatment with corticosteroids, especially at high oral doses, can cause several
      adverse effects, such as immunosuppression, diabetes, psychiatric disorders, osteoporosis,
      optic lesion and peptic ulcer. Thus, the use of local corticosteroid injection could minimize
      these side effects. However, local injection implies risks of bleeding and perforation, and
      is of limited use in patients receiving anticoagulant or antiplatelet therapy.

      The objective of this study was to compare the local corticosteroid injection and the use of
      oral corticosteroids to prevent stenosis after extensive submucosal endoscopic resection of
      superficial esophageal carcinoma, in relation to the stenosis rate, number of dilations
      necessary to resolve the stenosis and frequency of complications.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Early Stenosis rate
time frame: 12 weeks
description: Stenosis to the passage of the standard endoscopic (9.8 mm)
measure: Late Stenosis rate
time frame: 24 weeks
description: Stenosis to the passage of the standard endoscopic (9.8 mm)
measure: Early resistance rate
time frame: 12 weeks
description: Resistance to the passage of the standard endoscopic (9.8 mm)
measure: Late resistance rate
time frame: 24 weeks
description: Resistance to the passage of the standard endoscopic (9.8 mm)
measure: Number of dilations to solve the stenosis
time frame: 24 weeks
description: Number of endoscopic dilations (Savary or balloon)
measure: Complications
time frame: 24 weeks
description: Complications related to the procedure and preventive therapy.
arm group label: Local steroid-triamcinolone acetonide
arm group type: Experimental
description: Local steroid (triamcinolone acetonide) injection to the ulcer immediately after ESD. Total amount of injected triamcinolone is 100 mg.
arm group label: Oral steroid-predonisolone
arm group type: Active Comparator
description: (predonisolone) administration three days after ESD. Predonisolone is administered over 8 weeks, started at 30 mg/day and tapered 30, 30, 25, 25, 20, 15, 10 and 5 every 7 days, totaling 8 weeks of treatment.
intervention type: Drug
intervention name: Local steroid - triamcinolone acetonide
description: (triamcinolone acetonide)
arm group label: Local steroid-triamcinolone acetonide
intervention type: Drug
intervention name: Oral steroid - predonisolone
description: (predonisolone)
arm group label: Oral steroid-predonisolone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fauze Maluf-Filho, PhD
phone: 55 11 99191-9014
email: fauze.maluf@terra.com.br
last name: Joel F Oliveira, MD
phone: 55 11 96382-0289
email: jfoliveira1@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Brazil
responsible party type: Sponsor
mesh term: Esophageal Stenosis
mesh term: Constriction, Pathologic
mesh term: Triamcinolone
mesh term: Triamcinolone Acetonide
mesh term: Triamcinolone hexacetonide
mesh term: Triamcinolone diacetate
sharing ipd: No