Mebeverine and the Influence of Labeling in Adolescents With Irritable Bowel Syndrome or Functional Abdominal Pain Not Otherwise Specified: A 2 × 2 Randomized, Placebo-Controlled Trial.

Background & Aims: Pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified lack effective pharmacologic interventions. The efficacy of mebeverine, an antispasmodic agent, and the effect of labeling within a pediatric cohort were evaluated.

Methods: This randomized trial was conducted across 13 hospitals. Participants (12-17 years) with irritable bowel syndrome or functional abdominal pain-not otherwise specified received mebeverine (200 mg twice daily) or placebo for 8 weeks. Treatment was labeled as "mebeverine or placebo" (blinded trial label) or "mebeverine" (mebeverine label), creating the following 4 groups: (1) mebeverine-blinded trial label, (2) mebeverine-mebeverine label, (3) placebo-blinded trial label, and (4) placebo-mebeverine label. Randomization (1:1:1:1) was masked to physicians, except for drug labeling. Primary end point was treatment success (>50% reduction of abdominal pain intensity and frequency) after 8 weeks. The key secondary end point was adequate relief of symptoms.

Results: Of the 269 randomized patients, treatment success was similar between those receiving mebeverine (groups 1 and 2) (n = 31 [23.4%]) and placebo (groups 3 and 4) (n = 30 [22.0%]; odds ratio [OR], 1.08; 95% CI, 0.59-1.99; P = .81). Treatment success was higher in groups with the mebeverine label (groups 2 and 4) (n = 42 [31.6%]) compared with the blinded trial label (groups 1 and 3) (n = 19 [14.1%]; OR, 2.84; 95% CI, 1.52-5.34; P = .001). Adequate relief rates were similar between mebeverine (n = 55 [41.0%]) and placebo groups (n = 61 [45.5%]; OR, 0.83; 95% CI, 0.51-1.35; P = .46), but higher in mebeverine-labeled groups (n = 67 [50.4%]) compared with blinded trial-labeled groups (n = 49 [36.3%]; OR, 1.78; 95% CI, 1.1-2.9; P = .02). Adverse events were mild and infrequent.

Conclusions: Mebeverine was ineffective in treatment of pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified. However, a positive drug label significantly enhanced treatment outcomes compared with a blinded trial label. (International Clinical Trials Registry Platform, Number: NL-OMON55563.).