Trimebutine Maleate Combined With Rabeprazole in Patients With Grade A or B Reflux Esophagitis Whose Symptoms Refractory to Rabeprazole (rRE)

• ClinicalTrials.gov Identifier: NCT02986685
• Recruitment Status: Unknown
• First Posted: December 8, 2016
• Last Update Posted: December 8, 2016
• Sponsor: Xijing Hospital of Digestive Diseases
• Collaborators: Ankang City Central Hospital; Shaanxi Provincial People's Hospital; Baoji Central Hospital; Hanzhong Central Hospital
• Information provided by (Responsible Party): Yongquan Shi, Xijing Hospital of Digestive Diseases

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Refractory Reflux Esophagitis	Drug: Trimebutine Maleate; Drug: rabeprazole	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: November 2016
• Estimated Primary Completion Date: October 2017
• Estimated Study Completion Date: November 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: trimebutine maleate + rabeprazole; trimebutine maleate 200mg three times daily combined with rabeprazole 20mg once daily	Drug: Trimebutine Maleate; 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.; Drug: rabeprazole; 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.
rabeprazole; rabeprazole 20mg once daily	Drug: rabeprazole; 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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]

   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.

2. 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 ]

Secondary Outcome Measures :

1. change of GerdQ score from baseline to the end of 8 weeks [ Time Frame: baseline，the end of 8 weeks ]
   The results before and after treatment will be compared
2. 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 ]
   The results before and after treatment will be compared
3. change of Athens insomnia scale score from baseline to the end of 8 weeks [ Time Frame: baseline，the end of 8 weeks ]
   Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared
4. 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 ]
   Athens insomnia scale score was used to evaluate the quality of sleep. The results before and after treatment will be compared
5. change of WHOQOL-BREF score from baseline to the end of 8 weeks [ Time Frame: baseline ， the end of 8 weeks ]
   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
6. 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 ]
   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
7. change of HADS score from baseline to the end of 8 weeks [ Time Frame: baseline，the end of 8 weeks ]
   Depression and anxiety was assessed with HADS.The results before and after treatment will be compared
8. 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 ]
   Depression and anxiety was assessed with HADS.The results before and after treatment will be compared
9. change of the results of upper gastrointestinal endoscopy from baseline to the end of 12 weeks [ Time Frame: baseline,the end of 12 weeks ]
   If the patients complete the upper gastrointestinal endoscopy before and after the treatment,the results of the mucosal healing will be analyzed.
10. The dietary habits of the patients with refractory Los Angeles class A or B reflux esophagitis [ Time Frame: baseline ]
11. 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 ]
12. the smoking and alcohol drinking habits of the patients with refractory Los Angeles class A or B reflux esophagitis [ Time Frame: baseline ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients with typical symptoms of heartburn sensation, or acid regurgitation,or both for at least 6 months.The symptoms were moderate or severe and at least three days a week in 7 days prior to the enrollment,which can complicate with Atypical and extraesophageal symptoms .
2. Diagnosed by upper gastrointestinal endoscopy within one month before enrollment with grade A or B reflux esophagitis according to Los Angeles classification

Exclusion Criteria:

1. History of endoscopic anti-reflux surgery,Fundoplication and major gastrointestinal surgery.
2. History of the chest or abdominal radiotherapy.
3. History of grade C or D reflux esophagitis,other gastrointestinal diseases such as Barrett's esophagus,zollinger-ellison syndrome, gastric or duodenal ulcer(excluding ulcer scar),large (>5cm)hiatus hernia,malignant tumor,esophageal stricture,esophageal and gastric Varices,hemorrhage or perforation of the digestive tract,mechanical ileus,et al.
4. The presence of serious comorbidities (liver, gallbladder, pancreas, spleen,kidney,heart,lung,blood system,endocrine,mental disease,autoimmunity and metabolic disorders) and malignant tumor of other organs.
5. Diagnosis of endocrine,neurological and autoimmunity disorders that may seriously affect motility(e.g. scleroderma or gastroparesis),and the primary esophageal motility disorders(achalasia,esophagospasm or nutcracker oesophagus).
6. Pregnancy or lactation during the study and follow-up period.
7. Use of antisecretory drugs(PPIs or H2RA),eradication of H pylori,drugs influenced the gastrointestinal motility,anticholinergics ,antipsychotics and so on within 4 weeks before the study.
8. Contraindications to trimebutine maleate or rabeprazole.
9. Use of drugs have interaction with the study drugs （e.g. cisapride ,procainamide, clopidogrel or ciclosporin),or drugs which may affect the results of the study(e.g. antisecretory drugs(PPIs or H2RA),prokinetics,mucosal protective drugs or anticholinergics),or drugs absorbed depending on the acidity of the gastric fluid(e.g.ketoconazole or digoxin),or CYP3A4,CYP2C19 inhibitors during the study.
10. Patients inability or refuse to consent, unable to complete the questionnaire,and have poor compliance to the treatment.
11. patients participated in other clinical trial 3 months before the study.

Contacts and Locations

Contacts

Contact: Yongquan Shi, professor; 86-029-84771515; shiyquan@fmmu.edu.cn

Locations

China, Shaanxi

Xijing Hosipital of Digestive Disease; Recruiting

Xi'an, Shaanxi, China, 710032

Contact: Yongquan Shi, professor 86-029-84771515 shiyquan@fmmu.edu.cn

Sponsors and Collaborators

Xijing Hospital of Digestive Diseases

Ankang City Central Hospital

Shaanxi Provincial People's Hospital

Baoji Central Hospital

Hanzhong Central Hospital

More Information

• Responsible Party: Yongquan Shi, Professor of Digestive Diseases, Xijing Hospital of Digestive Diseases
• ClinicalTrials.gov Identifier: NCT02986685
• Other Study ID Numbers: KY-20162096-1
• First Posted: December 8, 2016
• Last Update Posted: December 8, 2016
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study completion

Keywords provided by Yongquan Shi, Xijing Hospital of Digestive Diseases:

Refractory reflux esophagitis; Rabeprazole; trimebutine maleate

Additional relevant MeSH terms:

Gastroesophageal Reflux; Esophagitis; Esophagitis, Peptic; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Rabeprazole; Trimebutine; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs