<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/NCT04499495</url>
  </required_header>
  <id_info>
    <org_study_id>000388</org_study_id>
    <nct_id>NCT04499495</nct_id>
  </id_info>
  <brief_title>Assessment of 5-Aminosalicylic Acid Prescription Patterns and Treatment Outcomes in Patients With Ulcerative Colitis in Korea</brief_title>
  <official_title>A Retrospective Study to Assess 5-Aminosalicylic Acid Prescription Patterns and Treatment Outcomes in Patients With Ulcerative Colitis in Korea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ferring Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ferring Pharmaceuticals</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>
      The prevalence of ulcerative colitis (UC), which is one of the inflammatory bowel diseases,&#xD;
      is known to be increasing and the majority of patients (≥ 85%) have experienced mild or&#xD;
      moderate severity.&#xD;
&#xD;
      5-Aminosalicylic acid (5-ASA), immunomodulator, or biologics, etc are prescribed to treat UC,&#xD;
      however 5-ASA is generally considered the first-line therapy. The recent UC treatment&#xD;
      guideline in Korea and the United States/ European Union (US/EU) have recommended higher&#xD;
      daily dose for patients with mild or moderate severity than the previous guidelines since&#xD;
      2017. Accordingly, it is assumed that the average daily treatment dose of 5-ASA would&#xD;
      increase in patients who were initially diagnosed with UC in real-world clinical practice in&#xD;
      Korea. However, there are not many studies evaluating the treatment patterns and health&#xD;
      outcomes of 5-ASA based on the recent treatment guideline in South Korea.&#xD;
&#xD;
      This study, hence, aims to investigate the impact of changes in daily dose of 5-ASA on the&#xD;
      treatment patterns and health outcomes such as recurrence rate, hospitalization rate, and&#xD;
      surgery rate in real world practice using Health Insurance Review and Assessment (HIRA)&#xD;
      claims database.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2021</start_date>
  <completion_date type="Actual">July 31, 2022</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in initial 3-months average daily dose of 5-ASA</measure>
    <time_frame>From prescription index date up to 3 months</time_frame>
    <description>Initial average daily dose is defined as the average dose of 5-ASA prescribed over the 3-month period following the first prescription date of 5-ASA (i.e. prescription index date). Dose of 5-ASA includes those of mesalamine, sulfasalazine, and balsalazide.&#xD;
The dose will be stratified by oral monotherapy, rectal monotherapy, oral and rectal combination therapy. Oral and rectal combination therapy will be identified when the percentage of rectal therapy over the 3-months following the first prescription date of 5-ASA is more than 25%. For oral and rectal combination therapy, only oral formulation will be considered to calculate the dose of a combination therapy.&#xD;
The average daily dose of 5-ASA will be categorized as: Oral mono high dose (&gt;=3g), oral mono standard dose (2-3g), oral mono low dose (&lt;2g); Oral combination high dose (&gt;=3g), oral combination standard dose (2-3g); oral combination low dose (&lt;2g); Rectal monotherapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prescription patterns of 5-ASA</measure>
    <time_frame>From 01 January 2009 to 31 March 2019</time_frame>
    <description>The prescription patterns will be categorized into: oral monotherapy; rectal monotherapy; oral and rectal combination therapy based on the exposure medications (mesalazine, sulfasalazine, and/or balsalazide) prescribed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-response to 5-ASA by the average daily dose of 5-ASA</measure>
    <time_frame>From 01 January 2009 to 31 March 2019</time_frame>
    <description>The non-response to 5-ASA is defined as: &gt;=1 claims with international statistical classification of diseases 10th revision (ICD-10) code for UC as primary diagnosis and with pre-defined medications prescribed to those who are not responsive to 5-ASA. Medications for non-response are defined as add-on or switching to steroids, immunosuppressants, and/or biologics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ulcerative Colitis Related hospitalization by the average daily dose of 5-ASA</measure>
    <time_frame>From 01 January 2009 to 31 March 2019</time_frame>
    <description>The hospitalization is defined as: &gt;=1 length of stay (days); admission to the department for gastroenterology; and at least one surgery code or UC medications. The UC surgery includes small bowel resection, colon resection, and/or low anterior resection, defined using surgery code. The UC medication is defined as moderate- to high-dose steroids, immunosuppressants, and/or biologics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ulcerative Colitis related surgery by the average daily dose of 5-ASA</measure>
    <time_frame>From 01 January 2009 to 31 March 2019</time_frame>
    <description>Surgeries include small bowel resection, colon resection, and/or low anterior resection, which will be identified using surgery code.</description>
  </secondary_outcome>
  <enrollment type="Actual">11385</enrollment>
  <condition>Ulcerative Colitis</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PENTASA (mesalamine/ 5-Aminosalicylic acid (5-ASA)</intervention_name>
    <description>The 5-ASAs of interest in the study are mesalazine (5-ASA); sulfasalazine (5-ASA+sulfapyridine); and balsalazide (5-ASA) and will be grouped together as 5-ASA. For sulfasalazine and balsalazide, the equivalent dose to 5-ASA will be calculated as: balsalazide 6.75g is equivalent to 2.4g of mesalamine; and Sulfasalazine 4g is equivalent to 1.6g of mesalamine.&#xD;
The dose will be stratified by oral monotherapy, rectal monotherapy, oral and rectal combination therapy.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be selected from Korean HIRA claim database according to the&#xD;
        inclusion/exclusion criteria. The Korean patients who were initially diagnosed with UC from&#xD;
        01 January 2009 to 30 June 2018 will be included in this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who were diagnosed with UC during the index period.&#xD;
&#xD;
          -  Patients who had at least two claims of 5-ASA (sulfasalazine, balsalazide, mesalamine)&#xD;
             during the index period.&#xD;
&#xD;
          -  Patients who underwent at least one endoscopy within a 3-month period prior to the&#xD;
             index date (i.e. the first date of diagnosis with UC).&#xD;
&#xD;
               -  Defined as a claim with relevant endoscopy procedure code.&#xD;
&#xD;
               -  Include the upper gastrointestinal endoscopy, colonoscopy, sigmoidoscopy, which&#xD;
                  are identified using the procedure code.&#xD;
&#xD;
          -  Patients who were treated with 5-ASA continuously for at least 1-month after the index&#xD;
             date.&#xD;
&#xD;
               -  Defined as those who were treated with 5-ASA for more than 30 days within 6-month&#xD;
                  after the index date (i.e. the first date of diagnosis with UC).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients less than 15 years old as of the index date (&lt;15 years old).&#xD;
&#xD;
          -  Patients who were treated with 5-ASA during the baseline period (i.e. 12-month prior&#xD;
             to the index date).&#xD;
&#xD;
          -  Patients who were diagnosed with UC during the baseline period.&#xD;
&#xD;
          -  Patients who received steroids, immunosuppressants, or biologics during the baseline&#xD;
             period.&#xD;
&#xD;
               -  Steroid includes both oral medication and intravenous (IV) injection. The&#xD;
                  analysis will include the moderate- to high-dose of cumulative steroid use, which&#xD;
                  is defined as &gt;=30mg of prednisolone, &gt;= 50mg of methylprednisolone, or &gt;=50mg of&#xD;
                  hydrocortisone.&#xD;
&#xD;
               -  Immunosuppressants is defined as at least one claim with Azathioprine or&#xD;
                  6-Mercaptopurine.&#xD;
&#xD;
               -  Biologics is defined as at least one claim with Infliximab, Adalimumab,&#xD;
                  Ustekinumab, Vedolizumab, Golimumab, or Tofacitinib.&#xD;
&#xD;
          -  Patients who were diagnosed with Crohn's disease at any time in the overall study&#xD;
             period.&#xD;
&#xD;
               -  Defined as a claim with relevant Crohn's disease code recorded as primary&#xD;
                  diagnosis during the baseline period or follow-up period (i.e. entire study&#xD;
                  period).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Compliance</last_name>
    <role>Study Director</role>
    <affiliation>Ferring Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <state>Seodaemun-gu</state>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>September 9, 2022</last_update_submitted>
  <last_update_submitted_qc>September 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mesalamine</keyword>
  <keyword>Retrospective</keyword>
  <keyword>5-aminosalicylic acid</keyword>
  <keyword>Prescription pattern</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aminosalicylic Acid</mesh_term>
    <mesh_term>Mesalamine</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/NCT04499495
org study id: 000388
nct id: NCT04499495
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The prevalence of ulcerative colitis (UC), which is one of the inflammatory bowel diseases,
      is known to be increasing and the majority of patients (≥ 85%) have experienced mild or
      moderate severity.

      5-Aminosalicylic acid (5-ASA), immunomodulator, or biologics, etc are prescribed to treat UC,
      however 5-ASA is generally considered the first-line therapy. The recent UC treatment
      guideline in Korea and the United States/ European Union (US/EU) have recommended higher
      daily dose for patients with mild or moderate severity than the previous guidelines since
      2017. Accordingly, it is assumed that the average daily treatment dose of 5-ASA would
      increase in patients who were initially diagnosed with UC in real-world clinical practice in
      Korea. However, there are not many studies evaluating the treatment patterns and health
      outcomes of 5-ASA based on the recent treatment guideline in South Korea.

      This study, hence, aims to investigate the impact of changes in daily dose of 5-ASA on the
      treatment patterns and health outcomes such as recurrence rate, hospitalization rate, and
      surgery rate in real world practice using Health Insurance Review and Assessment (HIRA)
      claims database.
observational model: Cohort
time perspective: Retrospective
measure: Changes in initial 3-months average daily dose of 5-ASA
time frame: From prescription index date up to 3 months
description: Initial average daily dose is defined as the average dose of 5-ASA prescribed over the 3-month period following the first prescription date of 5-ASA (i.e. prescription index date). Dose of 5-ASA includes those of mesalamine, sulfasalazine, and balsalazide.
The dose will be stratified by oral monotherapy, rectal monotherapy, oral and rectal combination therapy. Oral and rectal combination therapy will be identified when the percentage of rectal therapy over the 3-months following the first prescription date of 5-ASA is more than 25%. For oral and rectal combination therapy, only oral formulation will be considered to calculate the dose of a combination therapy.
The average daily dose of 5-ASA will be categorized as: Oral mono high dose (>=3g), oral mono standard dose (2-3g), oral mono low dose (<2g); Oral combination high dose (>=3g), oral combination standard dose (2-3g); oral combination low dose (<2g); Rectal monotherapy.
measure: Prescription patterns of 5-ASA
time frame: From 01 January 2009 to 31 March 2019
description: The prescription patterns will be categorized into: oral monotherapy; rectal monotherapy; oral and rectal combination therapy based on the exposure medications (mesalazine, sulfasalazine, and/or balsalazide) prescribed.
measure: Non-response to 5-ASA by the average daily dose of 5-ASA
time frame: From 01 January 2009 to 31 March 2019
description: The non-response to 5-ASA is defined as: >=1 claims with international statistical classification of diseases 10th revision (ICD-10) code for UC as primary diagnosis and with pre-defined medications prescribed to those who are not responsive to 5-ASA. Medications for non-response are defined as add-on or switching to steroids, immunosuppressants, and/or biologics.
measure: Ulcerative Colitis Related hospitalization by the average daily dose of 5-ASA
time frame: From 01 January 2009 to 31 March 2019
description: The hospitalization is defined as: >=1 length of stay (days); admission to the department for gastroenterology; and at least one surgery code or UC medications. The UC surgery includes small bowel resection, colon resection, and/or low anterior resection, defined using surgery code. The UC medication is defined as moderate- to high-dose steroids, immunosuppressants, and/or biologics.
measure: Ulcerative Colitis related surgery by the average daily dose of 5-ASA
time frame: From 01 January 2009 to 31 March 2019
description: Surgeries include small bowel resection, colon resection, and/or low anterior resection, which will be identified using surgery code.
intervention type: Other
intervention name: PENTASA (mesalamine/ 5-Aminosalicylic acid (5-ASA)
description: The 5-ASAs of interest in the study are mesalazine (5-ASA); sulfasalazine (5-ASA+sulfapyridine); and balsalazide (5-ASA) and will be grouped together as 5-ASA. For sulfasalazine and balsalazide, the equivalent dose to 5-ASA will be calculated as: balsalazide 6.75g is equivalent to 2.4g of mesalamine; and Sulfasalazine 4g is equivalent to 1.6g of mesalamine.
The dose will be stratified by oral monotherapy, rectal monotherapy, oral and rectal combination therapy.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: No
last name: Global Clinical Compliance
role: Study Director
affiliation: Ferring Pharmaceuticals
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Aminosalicylic Acid
mesh term: Mesalamine
sharing ipd: No