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J Gastroenterol. 2011 May;46(5):595-602. doi: 10.1007/s00535-011-0372-3. Epub 2011 Feb 26.

A randomized controlled trial of rebamipide plus rabeprazole for the healing of artificial ulcers after endoscopic submucosal dissection.

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Department of Gastroenterology, Kobe University, School of Medicine, Kobe, Japan.



Endoscopic submucosal dissection (ESD) is an increasingly common technique for the resection of early gastric cancers. Although 8 weeks of treatment with a proton pump inhibitor (PPI) reportedly heals most patients with ESD-derived artificial ulcers, it does not heal those with severe atrophic gastritis, for whom there is little data. This study examined whether healing rates of the latter especially were improved by the addition of the non-PPI mucosal healing agent rebamipide after ESD.


Patients were randomly assigned to two treatment groups for 8 weeks following ESD: patients in the PPI group received daily rabeprazole alone (20 mg), whereas those in the combination group received daily rabeprazole (20 mg) and rebamipide (300 mg). At the primary endpoint (56 days after ESD) we determined the proportion of patients in whom ulcers had healed to scar-stage (S-stage, complete healing). A pre-specified subgroup analysis examined ulcer healing in patients with severe atrophic gastritis.


Overall, progression to S-stage occurred in 54.8% in the PPI group, and 86.7% in the combination group (odds ratio 5.3, 95% confidence interval 1.50-19.02, p = 0.006). Among those patients with severe atrophic gastritis, healing to S-stage occurred in 30.0% in the PPI group, and in 92.9% in the combination group (odds ratio 30.3, 95% confidence interval 2.63-348.91, p = 0.0023).


Treatment with a PPI plus rebamipide improved healing rates at 8 weeks for patients with ESD-derived artificial ulcer, and appeared to be particularly effective for patients with severe atrophic gastritis.

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