Healing Effect of Rebamipide in Addition to Omeprazole for Gastric Ulcer: Preliminary Results of a Randomized, Double-blind, Placebo-controlled Trial

Abstract

Background: Rebamipide is a mucoprotective agent which has anti-oxidative and anti-inflammatory effects, as well as the ability to increase mucosal blood flow. From theoretical basis, addition of rebamipide to proton pump inhibitors (PPI) may facilitate the healing of gastric ulcer (GU). Objective: To compare the GU healing rates between treatment with a combination of rebamipide plus omeprazole and omeprazole monotherapy Materials and Methods: This double-blind, randomized, placebo-controlled trial was conducted at Rajavithi Hospital, Bangkok between 2018-2019. Patients with GU size 0.5-3 cm were randomly assigned into either combination group (omeprazole 20 mg OD + rebamipide 100 mg TID) or PPI monotherapy group (omeprazole 20 mg OD + placebo). Primary endpoint was healed GU after 4 weeks of treatment determined by follow-up esophagogastroduodenoscopy.   Results: A total of 70 patients were randomized and 64 completed the study. The proportion of patients with non-steroidal anti-inflammatory drugs (NSAIDs) use and Helicobacter pylori positive were 42.9% and 68.6% in the combination group, 62.9% and 60% in the PPI group, without statistically significant difference. Overall, healed GU occurred in 77.1% in the combination group, and 60% in the PPI group, as intention-to-treat analysis (p=0.198). Mean change of size of GU was -0.8 cm (-1, -0.60) in the combination group, and -0.68 cm (-0.81, -0.55) in the PPI group (p=0.3). In subgroups analysis, patients with the presence of H. pylori , atrophic gastritis and/or intestinal metaplasia, NSAIDs use and current smoking have higher rates of healed GU by the combination therapy compared with PPI alone (p>0.05). There were no differences in compliance and treatment side effects between the two groups. Conclusion: Treatment with rebamipide plus PPI has a trend toward improved GU healing, compared with PPI monotherapy, especially in subgroup of patients with features of difficult to heal GU (presence of H. pylori , atrophic gastritis, intestinal metaplasia, NSAIDs and smoking). Keywords: Gastric ulcer, Mucoprotective drug, Omeprazole, Peptic ulcer disease, Proton pump inhibitor, Rebamipide