A Study to Evaluate REbamiPide as an Adjuvant Regimen to Heal erosIve Reflux Esophagitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate whether Rebamipide facilitate the healing of inflamed mucosa as an adjuvant regimen in erosive reflux esophagitis (ERE).

Detailed Description
-----------------
To evaluate whether Rebamipide facilitate the healing of inflamed mucosa as an adjuvant regimen in erosive reflux esophagitis patients To evaluate the safety of rebamipide as an adjuvant regimen in erosive reflux esophagitis (ERE)

Official Title
-----------------
A Multicenter, Randomized, Double-blinded, Placebo-controlled Pilot Study to Evaluate the Efficacy and Safety of Rebamipide as an Adjuvant Regimen to Heal erosIve Reflux Esophagitis (REPAIR)

Conditions
-----------------
Gastroesophageal Reflux

Intervention / Treatment
-----------------
* Drug: Lansoprazole
* Drug: Rebamipide
* Drug: Rebamipide-placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male/female patients aged 20 to 70 at the time of writing an informed consent. Subjects who were diagnosed with Erosive Reflux Esophagitis (ERE) using Los Angeles (LA) classification grade A D, confirmed by endoscopy. The subjects regardless of presence of ERE symptom (i.e., symptomatic ERE or asymptomatic ERE). For symptomatic ERE, the subject must have one or more symptoms of the followings: acid regurgitation, heartburn, epigastric pain, cough, hoarseness, globus pharyngis, atypical chest pain. Subjects who have consented to participate in this clinical study by signing an informed consent form. Exclusion Criteria: Patients with known hypersensitivity to any component of Lanston® and/or Mucosta® formulations. Other concurrent organic upper gastroesophageal disease in endoscopy (i.e., drug-induced esophagitis, viral esophagitis, Mallory-Weiss syndrome, peptic ulcer disease, malignancies) and patients who was diagnosed with Barrett's esophagus. History of abdominal surgery that can affect gastrointestinal motility (except appendectomy and hysterectomy). History of upper gastrointestinal bleeding or obstruction. Patients administrated with any drugs that can affect the efficacy of study regimen (proton pump inhibitors, revaprazan, prokinetics, H2-blockers, etc.) within 2 weeks (however, 4 weeks for PPIs) prior to enrollment and/or those who are required of NSAIDs, anti-coagulants, anti-cholinergics, prostaglandin E, corticosteroids, and anti-depressants treatment during the study period. History of pancreatobiliary disease (except asymptomatic gallbladder stone), inflammatory bowel disease, cirrhotic liver disease, chronic kidney disease. Pregnant, nursing, and childbearing potential women who is unwilling to effective contraception; for example, oral contraceptives, hormonal methods, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods (i.e., condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilization, and true abstinence. History of psychological disorder, alcoholics, and drug abuser. Blood test results of hemoglobin (Hb) ≤ 10.0 g/dL, platelets ≤ 50,000 /µL, total WBCs ≤ 4,000/µL or ≥ 10,000/µL, and with serum test results showing the levels of AST, ALT, ALP, BUN, and creatinine exceeding twice the normal range of respective institution. Patients who previously underwent another clinical survey within 4 weeks. History of major medical disease that can affect general condition and other patients deemed not eligible for this study by investigators.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Lanston® (lansoprazole) 30 mg, 1 capsule, PO, qd, 30 min before breakfast Mucosta® (rebamipide) 100 mg, 1 tablet, PO, tid, 30 minutes before breakfast, lunch and dinner | Drug: Lansoprazole<br>* Oral administration of Lanston® (lansoprazole) 30 mg, 1 capsule, PO, qd, 30 min before breakfast<br>* Other names: Lanston;Drug: Rebamipide<br>* Oral administration of Mucosta (rebamipide) 100 mg, 1 tablet, PO, tid, 30 minutes before breakfast, lunch, and dinner<br>* Other names: Mucosta;|
| Placebo Comparator: Control Group<br>Lanston® (lansoprazole) 30 mg, 1 capsule, PO, qd, 30 min before breakfast Mucosta®-placebo (rebamipide-placebo), 1 tablet, PO, tid, 30 minutes before breakfast, lunch and dinner | Drug: Lansoprazole<br>* Oral administration of Lanston® (lansoprazole) 30 mg, 1 capsule, PO, qd, 30 min before breakfast<br>* Other names: Lanston;Drug: Rebamipide-placebo<br>* Oral administration of Mucosta®-placebo, 1 tablet, PO, tid, 30 minutes before breakfast, lunch and dinner<br>* Other names: Mucosta-placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic healing rate | The ratio of the endoscopically completely healed (normal or minimal change) patients per groups | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic change | Histologic change defined with Hematoxylin and eosin (H&E) stain | 4 weeks | 
| Change in inflammatory cytokines | Change in the tissue level of Platelet activating factor (PAF) and Interleukin-8 (IL-8) | 4 weeks | 
| Time to complete symptom relief | Interval between inital medication and the first time of symptom relief judged by subject's diary | every 2 week, up to 4 week | 
| Overall symptom relief | The proportion of relieved subjects at the end of treatment | every 2 week, up to 4 week | 
| Adverse events profile | patient's symptoms, physical findings, abnormal laboratory values, vital signs, and ECG findings | every 2 week, up to 4week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rebamipide