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

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

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.

Study Overview

• Status: Unknown
• Conditions: Refractory Reflux Esophagitis
• Intervention / Treatment: Drug: Trimebutine Maleate; Drug: rabeprazole

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yongquan Shi, professor; Phone Number: 86-029-84771515; Email: shiyquan@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hosipital of Digestive Disease
      • Contact: Yongquan Shi, professor; Phone Number: 86-029-84771515; Email: shiyquan@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of main symptom （heartburn，acid regurgitation，non-cardiac chestpain，hoarseness，et，al）score from baseline to 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.	baseline ，the end of 8 weeks
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		the end of 8 weeks ， the end of 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of GerdQ score from baseline to the end of 8 weeks	The results before and after treatment will be compared	baseline，the end of 8 weeks
change of GerdQ score from the end of 8 weeks to the end of 12 weeks	The results before and after treatment will be compared	the end of 8 weeks，the end of 12 weeks
change of Athens insomnia scale score from baseline to 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	baseline，the end of 8 weeks
change of Athens insomnia scale score from the end of 8 weeks to 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	the end of 8 weeks，the end of 12 weeks
change of WHOQOL-BREF score from baseline to 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	baseline ， the end of 8 weeks
change of WHOQOL-BREF score from the end of 8 weeks to 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	the end of 8 weeks， the end of 12 weeks
change of HADS score from baseline to the end of 8 weeks	Depression and anxiety was assessed with HADS.The results before and after treatment will be compared	baseline，the end of 8 weeks
change of HADS score from the end of 8 weeks to the end of 12 weeks	Depression and anxiety was assessed with HADS.The results before and after treatment will be compared	the end of 8 weeks , the end of 12 weeks
change of the results of upper gastrointestinal endoscopy from baseline to 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.	baseline,the end of 12 weeks
The dietary habits of the patients with refractory Los Angeles class A or B reflux esophagitis		baseline
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		baseline
the smoking and alcohol drinking habits of the patients with refractory Los Angeles class A or B reflux esophagitis		baseline

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases
• Collaborators: Shaanxi Provincial People's Hospital; Baoji Central Hospital; Hanzhong Central Hospital; Ankang City Central Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): November 1, 2017

Study Registration Dates

• First Submitted: November 23, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Rabeprazole; Refractory reflux esophagitis; trimebutine maleate
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Esophagitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole; Trimebutine
• Other Study ID Numbers: KY-20162096-1

Plan for Individual participant data (IPD)

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