Randomized Double-Blind Clinical Trial of Rebamipide vs Esomeprazole in the Treatment of NSAID-induced Gastropathy

Primary objective: To determine the levels of malondialdehyde (MDA) and immunohistochemistry surrogate of inflammation in patients with NSAID-induced gastric mucosal injury treated with Rebamipide 3x a day vs Esomeprazole 40mg once a day. Secondary objective: For patients who become symptomatic during NSAID treatment, to compare the proportion of patients with positive treatment effects using the Likert scale. Third objective: To compare the proportion of patients with positive treatment effects as determined by Modified Lanza scoring between the two groups.

Study Overview

• Status: Completed
• Conditions: NSAID Induced Gastropathy
• Intervention / Treatment: Drug: Rebamipide and Esomeprazole

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Philippines
  • Manila, Philippines
    • University of Santo Tomas Hospital
  • Quezon City, Philippines
    • Armed Forces of the Philippines Medical Center
  • Quezon City, Philippines
    • Veterans Memorial Medical Center
  • San Juan City, Philippines
    • Candinal Santos medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with rheumatoid arthritis and osteoarthritis who developed dyspeptic symptoms while on NSAID for at leat 4 weeks who fulfill any of the following criteria: 1) Have not been on NSAIDs (NSAID-naïve) as they are newly diagnosed patients or satisfies ALL of the following criteria: a) Have not received NSAIDs for more than 2 years continuously, b) Have not received NSAID for at least 3 months, c) Does not take more than the therapeutic dose required for any of the following NSAIDS: Aspirin (at max. 4000mg.day), Naproxen (at max. 1375mg/day), Ibupropen (at max. 2400mg/day), Diclofenac (at max. 200mg/day), Piroxicam (at max. 40mg/day). 2) Gastric mucosal lesions on upper endoscopy (Lanza score ≥ 1) 3) More than 18 and less than 65 years old 4) Medically cleared and consents to undergo upper endoscopy 5) Willing to participate in the trial and sign an informed consent form

Exclusion Criteria:

1. Patients with known malignancy 2) Women who are pregnant and breastfeeding 3) Psychiatric illness 4) severe co-morbid illness like renal failure, cirrhosis, etc. 5) History of intake of any anti-secretory agent for the past 2 weeks 6) Patients with coagulation disorders and hematologic problems 7) Complicated ulcers, i.e. bleeding, perforating, etc. 8) Patients with evidence of portal hypertension i.e. varices, portal gastropathy, etc. 9) History of gastric surgery 10) Patients on COX-2 inhibitors 11) Modified Lanza score of 0 12) Herbal medications or complementary alternative medicines (e.g. glucosamine chondroitisulfate, etc. 13) (+)H.pylori test by RUT (Rapid Urease Test) and biopsy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Rebamipide 100mg TID for 12 weeks	Drug: Rebamipide and Esomeprazole; Rebamipide 100mg TID for 12 weeks; Esomeprazole 40mg OD + Esomeprazole-matching placebo BID for 12 weeks
Active Comparator: 2; Esomeprazole 40mg OD + Esomeprazole-matching placebo BID for 12 weeks	Drug: Rebamipide and Esomeprazole; Rebamipide 100mg TID for 12 weeks; Esomeprazole 40mg OD + Esomeprazole-matching placebo BID for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the levels of MDA and immunohistochemistry surrogate of inflammation in patients with NSAID-induced gastric mucosal injury.	Throughout the study

Secondary Outcome Measures

Outcome Measure	Time Frame
For patients who become symptomatic during NSAID treatment, to compare the proportion of patients with positive treatment effects using the Likert scale	Throughout the study

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical, Inc., Philippines
• Investigators: Principal Investigator: Jose Sollano, MD, University of Santo Tomas Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 18, 2008
• First Submitted That Met QC Criteria: March 20, 2008
• First Posted (Estimate): March 21, 2008

Study Record Updates

• Last Update Posted (Estimate): August 24, 2011
• Last Update Submitted That Met QC Criteria: August 23, 2011
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protective Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antioxidants; Esomeprazole; Rebamipide
• Other Study ID Numbers: 037-PPB-0701i