Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial

Abstract

BackgroundRebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated.MethodsAfter a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo.ResultsAll recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = −1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from −334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen.ConclusionRebamipide does not protect against naproxen-induced gastric damage in healthy volunteers.Trial registrationClinicalTrials.gov, NCT02632812. Registered 14 December 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0472-x) contains supplementary material, which is available to authorized users.

Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances

“…However, in our study, these effects did not reach statistical significance, despite the fact that rebamipide was administered twice daily. These data are also in accordance with data published in healthy volunteers showing that rebamipide had no protective effects against naproxen-induced gastric damage [25]. It is known that rebamipide exhibits low aqueous solubility, has poor oral bioavailability, and has a short half-life [26,27], which could explain the relatively weak gastro-protective effects observed in our experiments.…”

Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO)

“…Several other molecules are being evaluated in experimental models, such as potential NSAID gastroprotectors, including allantoin and rebamipide. The latter was found to be as effective as misoprostol in preventing gastroduodenal lesions from aceclofenac, meloxicam and nabumetone [100], but not from naproxen [101], and better tolerated. However, there are still no data in the literature to validate its efficacy in preventing gastrointestinal damage from antiplatelet agents or anticoagulants.…”

“…The interaction between H. pylori infection and antiplatelet therapy also remains controversial [5,78,[82][83][84][85][86][87][88], and randomized prospective studies are required. Finally, there is no evidence on the efficacy of gastroprotective drugs other than PPIs in preventing damage from antiplatelet agents [91][92][93][94][95][96][97][98][99][100][101]. Our final recommendations are summarized in Table 4.…”

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

“…Potential NSAID gastroprotectors, including allantoin and rebamipide, are being evaluated. The latter was found to be as effective as misoprostol[ 136 ] but not in patients treated with naproxen[ 137 ], and better tolerated. However, there is still no evidence about their efficacy in preventing gastrointestinal damage from antiplatelet agents or anticoagulants.…”