Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment

J Tack, F Zerbib, K Blondeau, S B des Varannes, H Piessevaux, J Borovicka, F Mion, M Fox, A J Bredenoord, H Louis, S Dedrie, M Hoppenbrouwers, A Meulemans, A Rykx, L Thielemans, M Ruth, J Tack, F Zerbib, K Blondeau, S B des Varannes, H Piessevaux, J Borovicka, F Mion, M Fox, A J Bredenoord, H Louis, S Dedrie, M Hoppenbrouwers, A Meulemans, A Rykx, L Thielemans, M Ruth

Abstract

Background: Approximately, 20-30% of patients with gastro-esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5-HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI.

Methods: This was a phase II, exploratory, multicenter, randomized, placebo-controlled, double-blind, parallel-group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires.

Key results: In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid-containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed.

Conclusions & inferences: No clear differences were seen in reflux parameters between the placebo and revexepride groups.

Keywords: 5-HT4 receptor agonist; gastro-esophageal reflux disease; prokinetic; reflux esophagitis; revexepride.

© 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Changes in the primary pharmacodynamic endpoints per 24 h from baseline to day 28 in the revexepride 0.5 mg t.i.d. and placebo groups: (A) mean (SD) number of liquid-containing reflux events; (B) mean (SD) proximal extent of liquid-containing reflux events; and (C) mean (SD) bolus clearance time of liquid-containing reflux events (pharmacodynamic population). Note that differences in the changes from baseline to day 28 between placebo and revexepride groups were not significant. SD, standard deviation; t.i.d., three times daily.
Figure 2
Figure 2
Mean (SD) number of daily occurrences of: (A) heartburn; (B) regurgitation; and (C) heartburn and/or regurgitation, during the run-in and at week 4 as reported in e-diaries. n = 28–31. Note that differences in the changes from baseline to week 4 between placebo and revexepride groups were not significant. SD, standard deviation; t.i.d., three times daily.

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Source: PubMed

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