<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/NCT02202967</url>
  </required_header>
  <id_info>
    <org_study_id>GN09CA403</org_study_id>
    <secondary_id>2013-003187-31</secondary_id>
    <nct_id>NCT02202967</nct_id>
  </id_info>
  <brief_title>Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs</brief_title>
  <acronym>MASTERS</acronym>
  <official_title>Misoprostol for the Healing of Small Bowel Ulceration in Patients With Obscure Blood Loss While Taking Low-dose Aspirin or Nonsteroidal Antiinflammatory Drugs [MASTERS Trial]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NHS Greater Glasgow and Clyde</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Anti-inflammatory tablets (non-steroidal anti-inflammatory drugs) continue to be used&#xD;
      commonly worldwide to relieve pain caused by arthritis. Likewise, aspirin is used by many&#xD;
      patients in order to prevent blood clots. Despite their desired benefits, these medicines can&#xD;
      cause internal bleeding from the digestive system. The source of this bleeding can be obvious&#xD;
      (overt), or obscure and thought to come from the small intestine. Obscure bleeding can show&#xD;
      as anemia due to lack of iron in the blood. Small intestine ulcers are now easily diagnosed&#xD;
      using an endoscope the size of a big pill (video capsule endoscopy). Small bowel ulcers are&#xD;
      not related to stomach acid and therefore do not heal using remedies usually taken to stop&#xD;
      acid formation. A different drug, misoprostol, consists of a chemical (prostaglandin) that is&#xD;
      usually lacking in patients using aspirin or anti-inflammatory drugs. Misoprostol is licenced&#xD;
      to heal stomach and duodenal ulcers in patients using these drugs. Our hypothesis is that&#xD;
      misoprostol might be effective in healing small bowel ulcers as suggested by pilot studies;&#xD;
      however, such works only included small numbers of patients, did not include control groups&#xD;
      and both patients and investigators knew the nature of the tablets used. To test this&#xD;
      hypothesis, we propose to compare misoprostol to a dummy tablet. The numbers of subjects to&#xD;
      be studied have been calculated using established statistical methods&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      METHODOLOGY:&#xD;
&#xD;
        -  Upper gastrointestinal endoscopy and colonoscopy on patients with obscure bleeding and/&#xD;
           or iron deficiency anemia.&#xD;
&#xD;
        -  Video capsule endoscopy on those fulfilling the inclusion criteria&#xD;
&#xD;
        -  Randomization to Misoprostol 200 micrograms or placebo, 4 times each day given for 8&#xD;
           weeks to aspirin/ NSAID users with erosive small bowel lesions.&#xD;
&#xD;
        -  Video capsule endoscopy at 8 weeks to check healing of small bowel lesions.&#xD;
&#xD;
        -  Full blood count at baseline and monthly intervals (0, 4, and 8 weeks)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 7, 2016</start_date>
  <completion_date type="Actual">October 11, 2017</completion_date>
  <primary_completion_date type="Actual">October 11, 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs.</measure>
    <time_frame>8 weeks</time_frame>
    <description>Ulcers or smaller lesions (erosions) should totally disappear by the end of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the numbers of mucosal ulcers and erosions</measure>
    <time_frame>8 weeks</time_frame>
    <description>Any increase or decrease in the numbers of ulcers and erosions will be measured at the end of the study</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in blood haemoglobin level</measure>
    <time_frame>8 weeks</time_frame>
    <description>Any rise or drop in the haemoglobin level will be measured at the end of the study</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Chronic Arthritis</condition>
  <condition>Ischemic Heart Disease</condition>
  <condition>Atrial Fibrillation</condition>
  <condition>Anemia</condition>
  <condition>Bleeding</condition>
  <arm_group>
    <arm_group_label>Misoprostol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Misoprostol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Misoprostol</intervention_name>
    <description>Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog</description>
    <arm_group_label>Misoprostol</arm_group_label>
    <other_name>Cytotec (R)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo contains lactose granules</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Dummy drug</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
        Obscure occult gastrointestinal bleeding: presence of one or more of the following:&#xD;
&#xD;
          -  Positive fecal occult blood test within last 3 months&#xD;
&#xD;
          -  Iron deficiency anemia (ferritin &lt;100 ug/l, hemoglobin [Hb] 7-12 g/dl [female] or 7-13&#xD;
             g/dl [male])&#xD;
&#xD;
          -  Drop in haemoglobin, &gt; 2gm/dl from baseline, in the absence of potential or actively&#xD;
             bleeding lesion detectable on upper endoscopy or colonoscopy.&#xD;
&#xD;
        Normal/ absence of potentially bleeding lesions on full upper endoscopy and colonoscopy.&#xD;
&#xD;
        Taking low-dose aspirin (75-325m/ day) and/ or NSAIDs&#xD;
&#xD;
        MAIN EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Incomplete upper endoscopy or colonoscopy&#xD;
&#xD;
          -  Systemic disease that is unstable at the time of randomisation (unstable vital signs;&#xD;
             ongoing non-gastrointestinal investigations; frequent modifications to treatment)&#xD;
&#xD;
          -  Intake of certain drugs: high-dose steroids (&gt;7.5-mg prednisolone/ day), cytotoxic&#xD;
             drugs, or warfarin.&#xD;
&#xD;
          -  Upper gastrointestinal lesions: oesophageal varices; oesophageal stricture;&#xD;
             oesophageal or gastric neoplasms; pyloric stenosis; peptic ulcers; vascular&#xD;
             malformations.&#xD;
&#xD;
          -  Colonic disorders: neoplasms or adenomatous polyps; inflammatory bowel disease;&#xD;
             vascular malformations; actively bleeding diverticular disease&#xD;
&#xD;
          -  Women planning pregnancy, pregnant or women of child-bearing potential not using two&#xD;
             contraceptive methods, one of which must be highly effective [implants, injectables,&#xD;
             combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or&#xD;
             vasectomised partner]&#xD;
&#xD;
          -  Hypotension: systolic blood pressure &lt;100-mm Hg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maureen Travers, PhD</last_name>
    <role>Study Director</role>
    <affiliation>NHS Greater Glasgow &amp; Clyde, Scotland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Crosshouse</name>
      <address>
        <city>Kilmarnock</city>
        <state>Scotland</state>
        <zip>KA2 0BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://dx.doi.org/10.1016/S2468-1253(18)30119-5</url>
    <description>Taha AS et al. MASTERS Trial.Lancet Gastroenterol Hepatol 2018;3:469-76</description>
  </link>
  <results_reference>
    <citation>Taha AS, McCloskey C, McSkimming P, McConnachie A. Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):469-476. doi: 10.1016/S2468-1253(18)30119-5. Epub 2018 May 10.</citation>
    <PMID>29754836</PMID>
  </results_reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 26, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>August 12, 2018</last_update_submitted>
  <last_update_submitted_qc>August 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aspirin</keyword>
  <keyword>Intestinal bleeding</keyword>
  <keyword>Misoprostol</keyword>
  <keyword>NSAIDs</keyword>
  <keyword>Small intestine</keyword>
  <keyword>Video capsule endoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Misoprostol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02202967
org study id: GN09CA403
secondary id: 2013-003187-31
nct id: NCT02202967
lead sponsor: 
has dmc: Yes
Anti-inflammatory tablets (non-steroidal anti-inflammatory drugs) continue to be used
      commonly worldwide to relieve pain caused by arthritis. Likewise, aspirin is used by many
      patients in order to prevent blood clots. Despite their desired benefits, these medicines can
      cause internal bleeding from the digestive system. The source of this bleeding can be obvious
      (overt), or obscure and thought to come from the small intestine. Obscure bleeding can show
      as anemia due to lack of iron in the blood. Small intestine ulcers are now easily diagnosed
      using an endoscope the size of a big pill (video capsule endoscopy). Small bowel ulcers are
      not related to stomach acid and therefore do not heal using remedies usually taken to stop
      acid formation. A different drug, misoprostol, consists of a chemical (prostaglandin) that is
      usually lacking in patients using aspirin or anti-inflammatory drugs. Misoprostol is licenced
      to heal stomach and duodenal ulcers in patients using these drugs. Our hypothesis is that
      misoprostol might be effective in healing small bowel ulcers as suggested by pilot studies;
      however, such works only included small numbers of patients, did not include control groups
      and both patients and investigators knew the nature of the tablets used. To test this
      hypothesis, we propose to compare misoprostol to a dummy tablet. The numbers of subjects to
      be studied have been calculated using established statistical methods
METHODOLOGY:

        -  Upper gastrointestinal endoscopy and colonoscopy on patients with obscure bleeding and/
           or iron deficiency anemia.

        -  Video capsule endoscopy on those fulfilling the inclusion criteria

        -  Randomization to Misoprostol 200 micrograms or placebo, 4 times each day given for 8
           weeks to aspirin/ NSAID users with erosive small bowel lesions.

        -  Video capsule endoscopy at 8 weeks to check healing of small bowel lesions.

        -  Full blood count at baseline and monthly intervals (0, 4, and 8 weeks)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs.
time frame: 8 weeks
description: Ulcers or smaller lesions (erosions) should totally disappear by the end of the study
measure: Change in the numbers of mucosal ulcers and erosions
time frame: 8 weeks
description: Any increase or decrease in the numbers of ulcers and erosions will be measured at the end of the study
measure: Change in blood haemoglobin level
time frame: 8 weeks
description: Any rise or drop in the haemoglobin level will be measured at the end of the study
arm group label: Misoprostol
arm group type: Active Comparator
description: Misoprostol
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Misoprostol
description: Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog
arm group label: Misoprostol
other name: Cytotec (R)
intervention type: Drug
intervention name: Placebo
description: Placebo contains lactose granules
arm group label: Placebo
other name: Dummy drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Maureen Travers, PhD
role: Study Director
affiliation: NHS Greater Glasgow & Clyde, Scotland
facility: 
country: United Kingdom
url: http://dx.doi.org/10.1016/S2468-1253(18)30119-5
description: Taha AS et al. MASTERS Trial.Lancet Gastroenterol Hepatol 2018;3:469-76
citation: Taha AS, McCloskey C, McSkimming P, McConnachie A. Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):469-476. doi: 10.1016/S2468-1253(18)30119-5. Epub 2018 May 10.
PMID: 29754836
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Heart Diseases
mesh term: Myocardial Ischemia
mesh term: Coronary Artery Disease
mesh term: Hemorrhage
mesh term: Misoprostol
sharing ipd: Undecided