<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/NCT02986685</url>
  </required_header>
  <id_info>
    <org_study_id>KY-20162096-1</org_study_id>
    <nct_id>NCT02986685</nct_id>
  </id_info>
  <brief_title>Trimebutine Maleate Combined With Rabeprazole in Patients With Grade A or B Reflux Esophagitis Whose Symptoms Refractory to Rabeprazole</brief_title>
  <acronym>rRE</acronym>
  <official_title>The Clinical Efficacy and Safety of Trimebutine Maleate Combined With Rabeprazole in Patients With Grade A or B Reflux Esophagitis Whose Symptoms Refractory to Rabeprazole</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xijing Hospital of Digestive Diseases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ankang City Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shaanxi Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baoji Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hanzhong Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Xijing Hospital of Digestive Diseases</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The research aims to investigate whether trimebutine maleate combined with rabeprazole can&#xD;
      improve the clinical efficacy in patients With refractory Los Angeles grade A or B reflux&#xD;
      esophagitis . A total of 500 patients with Grade A or B reflux esophagitis refractory to&#xD;
      rabeprazole will be randomly divided into two groups.One will continue to receive rabeprazole&#xD;
      treatment,and the other group will receive extra oral trimebutine maleate 200 mg three times&#xD;
      daily for 4 weeks. The end of the study for every patient is the improvement of main&#xD;
      symptoms. The primary and secondary analyses are the main symptoms score, endoscopy results,&#xD;
      Gastroesophageal reflux disease questionnaire（GerdQ) score,Hospital Anxiety and Depression&#xD;
      Scale(HADS) score, Athens insomnia scale and World Health Organization Quality of&#xD;
      Life-Bref(WHOQOL-BREF)scale scores at the baseline and final assessments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funds&#xD;
  </why_stopped>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">November 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2017</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>The change of main symptom （heartburn，acid regurgitation，non-cardiac chestpain，hoarseness，et，al）score from baseline to the end of 8 weeks</measure>
    <time_frame>baseline ，the end of 8 weeks</time_frame>
    <description>After the screening,the investigators defined the patients with main symptom score improvement less than 50% as the refractory reflux esophagitis patients.&#xD;
The results before and after treatment will be compared.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The change of main symptom （heartburn，acid regurgitation，non-cardiac chestpain，hoarseness，et，al）score from the end of 8 weeks to the end of 12 weeks</measure>
    <time_frame>the end of 8 weeks ， the end of 12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>change of GerdQ score from baseline to the end of 8 weeks</measure>
    <time_frame>baseline，the end of 8 weeks</time_frame>
    <description>The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of GerdQ score from the end of 8 weeks to the end of 12 weeks</measure>
    <time_frame>the end of 8 weeks，the end of 12 weeks</time_frame>
    <description>The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of Athens insomnia scale score from baseline to the end of 8 weeks</measure>
    <time_frame>baseline，the end of 8 weeks</time_frame>
    <description>Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of Athens insomnia scale score from the end of 8 weeks to the end of 12 weeks</measure>
    <time_frame>the end of 8 weeks，the end of 12 weeks</time_frame>
    <description>Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of WHOQOL-BREF score from baseline to the end of 8 weeks</measure>
    <time_frame>baseline ， the end of 8 weeks</time_frame>
    <description>The quality of life for the refractory reflux esophagitis patients was assessed with the WHOQOL-BREF.The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of WHOQOL-BREF score from the end of 8 weeks to the end of 12 weeks</measure>
    <time_frame>the end of 8 weeks， the end of 12 weeks</time_frame>
    <description>The quality of life for the refractory reflux esophagitis patients was assessed with the WHOQOL-BREF.The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of HADS score from baseline to the end of 8 weeks</measure>
    <time_frame>baseline，the end of 8 weeks</time_frame>
    <description>Depression and anxiety was assessed with HADS.The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of HADS score from the end of 8 weeks to the end of 12 weeks</measure>
    <time_frame>the end of 8 weeks , the end of 12 weeks</time_frame>
    <description>Depression and anxiety was assessed with HADS.The results before and after treatment will be compared</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of the results of upper gastrointestinal endoscopy from baseline to the end of 12 weeks</measure>
    <time_frame>baseline,the end of 12 weeks</time_frame>
    <description>If the patients complete the upper gastrointestinal endoscopy before and after the treatment,the results of the mucosal healing will be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The dietary habits of the patients with refractory Los Angeles class A or B reflux esophagitis</measure>
    <time_frame>baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The comorbidities（e.g.,hypertension，chronic kidney disease，diabetes，IBS,Functional dyspepsia,et，al） of the patients with refractory Los Angeles class A or B reflux esophagitis</measure>
    <time_frame>baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the smoking and alcohol drinking habits of the patients with refractory Los Angeles class A or B reflux esophagitis</measure>
    <time_frame>baseline</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Refractory Reflux Esophagitis</condition>
  <arm_group>
    <arm_group_label>trimebutine maleate + rabeprazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>trimebutine maleate 200mg three times daily combined with rabeprazole 20mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rabeprazole</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>rabeprazole 20mg once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trimebutine Maleate</intervention_name>
    <description>Rabeprazole 20mg once daily was administered during the 8 weeks' screening stage ,then oral trimebutine maleate 200mg three times daily combined with rabeprazole 20mg once daily were administered to the experimental arm for 4 weeks.</description>
    <arm_group_label>trimebutine maleate + rabeprazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rabeprazole</intervention_name>
    <description>Rabeprazole 20mg once daily was administered during the 8 weeks' screening stage,and rabeprazole 20mg once daily was administered to other arm for additional 4 weeks.</description>
    <arm_group_label>rabeprazole</arm_group_label>
    <arm_group_label>trimebutine maleate + rabeprazole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with typical symptoms of heartburn sensation, or acid regurgitation,or both&#xD;
             for at least 6 months.The symptoms were moderate or severe and at least three days a&#xD;
             week in 7 days prior to the enrollment,which can complicate with Atypical and&#xD;
             extraesophageal symptoms .&#xD;
&#xD;
          2. Diagnosed by upper gastrointestinal endoscopy within one month before enrollment with&#xD;
             grade A or B reflux esophagitis according to Los Angeles classification&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of endoscopic anti-reflux surgery,Fundoplication and major gastrointestinal&#xD;
             surgery.&#xD;
&#xD;
          2. History of the chest or abdominal radiotherapy.&#xD;
&#xD;
          3. History of grade C or D reflux esophagitis,other gastrointestinal diseases such as&#xD;
             Barrett's esophagus,zollinger-ellison syndrome, gastric or duodenal ulcer(excluding&#xD;
             ulcer scar),large (&gt;5cm)hiatus hernia,malignant tumor,esophageal stricture,esophageal&#xD;
             and gastric Varices,hemorrhage or perforation of the digestive tract,mechanical&#xD;
             ileus,et al.&#xD;
&#xD;
          4. The presence of serious comorbidities (liver, gallbladder, pancreas,&#xD;
             spleen,kidney,heart,lung,blood system,endocrine,mental disease,autoimmunity and&#xD;
             metabolic disorders) and malignant tumor of other organs.&#xD;
&#xD;
          5. Diagnosis of endocrine,neurological and autoimmunity disorders that may seriously&#xD;
             affect motility(e.g. scleroderma or gastroparesis),and the primary esophageal motility&#xD;
             disorders(achalasia,esophagospasm or nutcracker oesophagus).&#xD;
&#xD;
          6. Pregnancy or lactation during the study and follow-up period.&#xD;
&#xD;
          7. Use of antisecretory drugs(PPIs or H2RA),eradication of H pylori,drugs influenced the&#xD;
             gastrointestinal motility,anticholinergics ,antipsychotics and so on within 4 weeks&#xD;
             before the study.&#xD;
&#xD;
          8. Contraindications to trimebutine maleate or rabeprazole.&#xD;
&#xD;
          9. Use of drugs have interaction with the study drugs （e.g. cisapride ,procainamide,&#xD;
             clopidogrel or ciclosporin),or drugs which may affect the results of the study(e.g.&#xD;
             antisecretory drugs(PPIs or H2RA),prokinetics,mucosal protective drugs or&#xD;
             anticholinergics),or drugs absorbed depending on the acidity of the gastric&#xD;
             fluid(e.g.ketoconazole or digoxin),or CYP3A4,CYP2C19 inhibitors during the study.&#xD;
&#xD;
         10. Patients inability or refuse to consent, unable to complete the questionnaire,and have&#xD;
             poor compliance to the treatment.&#xD;
&#xD;
         11. patients participated in other clinical trial 3 months before the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Xijing Hosipital of Digestive Disease</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>January 30, 2023</last_update_submitted>
  <last_update_submitted_qc>January 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xijing Hospital of Digestive Diseases</investigator_affiliation>
    <investigator_full_name>Yongquan Shi</investigator_full_name>
    <investigator_title>Professor of Digestive Diseases</investigator_title>
  </responsible_party>
  <keyword>Refractory reflux esophagitis</keyword>
  <keyword>Rabeprazole</keyword>
  <keyword>trimebutine maleate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
    <mesh_term>Esophagitis</mesh_term>
    <mesh_term>Esophagitis, Peptic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rabeprazole</mesh_term>
    <mesh_term>Trimebutine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study completion</ipd_description>
  </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/NCT02986685
org study id: KY-20162096-1
nct id: NCT02986685
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The research aims to investigate whether trimebutine maleate combined with rabeprazole can
      improve the clinical efficacy in patients With refractory Los Angeles grade A or B reflux
      esophagitis . A total of 500 patients with Grade A or B reflux esophagitis refractory to
      rabeprazole will be randomly divided into two groups.One will continue to receive rabeprazole
      treatment,and the other group will receive extra oral trimebutine maleate 200 mg three times
      daily for 4 weeks. The end of the study for every patient is the improvement of main
      symptoms. The primary and secondary analyses are the main symptoms score, endoscopy results,
      Gastroesophageal reflux disease questionnaire（GerdQ) score,Hospital Anxiety and Depression
      Scale(HADS) score, Athens insomnia scale and World Health Organization Quality of
      Life-Bref(WHOQOL-BREF)scale scores at the baseline and final assessments.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The change of main symptom （heartburn，acid regurgitation，non-cardiac chestpain，hoarseness，et，al）score from baseline to the end of 8 weeks
time frame: baseline ，the end of 8 weeks
description: After the screening,the investigators defined the patients with main symptom score improvement less than 50% as the refractory reflux esophagitis patients.
The results before and after treatment will be compared.
measure: The change of main symptom （heartburn，acid regurgitation，non-cardiac chestpain，hoarseness，et，al）score from the end of 8 weeks to the end of 12 weeks
time frame: the end of 8 weeks ， the end of 12 weeks
measure: change of GerdQ score from baseline to the end of 8 weeks
time frame: baseline，the end of 8 weeks
description: The results before and after treatment will be compared
measure: change of GerdQ score from the end of 8 weeks to the end of 12 weeks
time frame: the end of 8 weeks，the end of 12 weeks
description: The results before and after treatment will be compared
measure: change of Athens insomnia scale score from baseline to the end of 8 weeks
time frame: baseline，the end of 8 weeks
description: Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared
measure: change of Athens insomnia scale score from the end of 8 weeks to the end of 12 weeks
time frame: the end of 8 weeks，the end of 12 weeks
description: Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared
measure: change of WHOQOL-BREF score from baseline to the end of 8 weeks
time frame: baseline ， the end of 8 weeks
description: The quality of life for the refractory reflux esophagitis patients was assessed with the WHOQOL-BREF.The results before and after treatment will be compared
measure: change of WHOQOL-BREF score from the end of 8 weeks to the end of 12 weeks
time frame: the end of 8 weeks， the end of 12 weeks
description: The quality of life for the refractory reflux esophagitis patients was assessed with the WHOQOL-BREF.The results before and after treatment will be compared
measure: change of HADS score from baseline to the end of 8 weeks
time frame: baseline，the end of 8 weeks
description: Depression and anxiety was assessed with HADS.The results before and after treatment will be compared
measure: change of HADS score from the end of 8 weeks to the end of 12 weeks
time frame: the end of 8 weeks , the end of 12 weeks
description: Depression and anxiety was assessed with HADS.The results before and after treatment will be compared
measure: change of the results of upper gastrointestinal endoscopy from baseline to the end of 12 weeks
time frame: baseline,the end of 12 weeks
description: If the patients complete the upper gastrointestinal endoscopy before and after the treatment,the results of the mucosal healing will be analyzed.
measure: The dietary habits of the patients with refractory Los Angeles class A or B reflux esophagitis
time frame: baseline
measure: The comorbidities（e.g.,hypertension，chronic kidney disease，diabetes，IBS,Functional dyspepsia,et，al） of the patients with refractory Los Angeles class A or B reflux esophagitis
time frame: baseline
measure: the smoking and alcohol drinking habits of the patients with refractory Los Angeles class A or B reflux esophagitis
time frame: baseline
arm group label: trimebutine maleate + rabeprazole
arm group type: Experimental
description: trimebutine maleate 200mg three times daily combined with rabeprazole 20mg once daily
arm group label: rabeprazole
arm group type: Other
description: rabeprazole 20mg once daily
intervention type: Drug
intervention name: Trimebutine Maleate
description: Rabeprazole 20mg once daily was administered during the 8 weeks' screening stage ,then oral trimebutine maleate 200mg three times daily combined with rabeprazole 20mg once daily were administered to the experimental arm for 4 weeks.
arm group label: trimebutine maleate + rabeprazole
intervention type: Drug
intervention name: rabeprazole
description: Rabeprazole 20mg once daily was administered during the 8 weeks' screening stage,and rabeprazole 20mg once daily was administered to other arm for additional 4 weeks.
arm group label: rabeprazole
arm group label: trimebutine maleate + rabeprazole
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Xijing Hospital of Digestive Diseases
investigator full name: Yongquan Shi
investigator title: Professor of Digestive Diseases
mesh term: Gastroesophageal Reflux
mesh term: Esophagitis
mesh term: Esophagitis, Peptic
mesh term: Rabeprazole
mesh term: Trimebutine
sharing ipd: No
ipd description: De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study completion