MEBEVERINE VERSUS PLACEBO IN ADOLESCENTS WITH IRRITABLE BOWEL SYNDROME OR FUNCTIONAL ABDOMINAL PAIN AND THE INFLUENCE OF LABELING: A 2X2 RANDOMIZED CONTROLLED TRIAL.

Abstract
Background: Effective and safe pharmacologic treatments are lacking for children with Irritable Bowel Syndrome (IBS) and Functional Abdominal Pain – Not otherwise specified (FAP-NOS). We evaluated the efficacy and safety of mebeverine, an antispasmodic agent. In addition, the effect of labeling on mebeverine and placebo was investigated.
Methods: In this placebo controlled, double blind, randomized trial 269 children (aged 12-18 years old) with IBS or FAP-NOS were assigned to mebeverine (at a dose of 200 mg twice daily) or placebo for 8 weeks and 4 weeks follow-up. Study medication was labeled as “you may receive mebeverine or placebo” (blinded trial label) or “you receive mebeverine” (mebeverine label), thus creating four treatment groups: 1) mebeverine with a blinded trial label, 2) mebeverine with a mebeverine label, 3) placebo with a blinded trial label and 4) placebo with a mebeverine label. The primary end point was the proportion of patients who achieved treatment success (a ≥50% reduction of both abdominal pain intensity and pain frequency) after 8 weeks. The key secondary outcome measure was adequate relief of IBS/FAP-NOS symptoms.
Results: Treatment success was similar between patients receiving mebeverine (group 1 and 2) and placebo (group 3 and 4) (23.9% vs. 23.9%, P=0.92). Significantly more patients in treatment groups with mebeverine label (group 2 and 4) achieved treatment success compared to treatment groups with blinded trial label (group 1 and 3) (32.9% vs. 15.0%, P=0.002). Similar proportions of patients receiving mebeverine (group 1 and 2) or placebo (group 3 and 4) reported adequate relief of their IBS/FAP-NOS symptoms (43.7% vs. 47.3% P=0.52). Significant more patients in treatment groups with mebeverine label (group 2 and 4) reached adequate relief than patients in treatment groups with blinded trial label (group 1 and 3) (52.8% vs. 38.3% P=0.02). Adverse events were infrequent and equal between groups.
Conclusions: Mebeverine was not superior compared to placebo for the treatment of pediatric IBS and FAP-NOS. However, being convinced to receive mebeverine enhanced treatment success and adequate relief rates significantly compared to not knowing. This may have implications for future pediatric drug trials.