Exploratory Study of Tegaserod for Dyspepsia in Women Receiving PPIs for Heartburn.

BACKGROUND AND AIMS: Tegaserod is a selective serotonin receptor (5-HT(4)) agonist that relieves dysmotility symptoms associated with constipation. Here we explore its effects on functional dyspepsia symptoms and heartburn during continued proton pump inhibitor (PPI) treatment. METHODS: In this multicenter pilot study, following a 2-week screening/baseline period, women with functional dyspepsia and persisting heartburn treated with PPIs received add-on open-label tegaserod 6 mg twice daily (bid) for 4 weeks. Treatment responders were then randomized 1:1 to continue double-blind tegaserod or placebo therapy for 6 weeks. Efficacy variables included the proportion of days with satisfactory relief of dyspepsia symptoms (early satiety, postprandial fullness and bloating) as well as the change in individual symptom severity scores for these three cardinal dyspepsia symptoms. Health-related quality of life was evaluated using a validated questionnaire, the Nepean Dyspepsia Index. Adverse events (AEs) were monitored. RESULTS: Of 101 women enrolled, 71 completed open-label treatment, and 70 responders were randomized to double-blind treatment. The proportion of days with satisfactory relief of dyspepsia symptoms (least squares mean, LSM) increased with tegaserod and placebo, to 0.69 and 0.62, respectively at study end (P = 0.366). Similarly, both groups showed improvements in the composite daily symptom severity score (overall LSM change from baseline of 1.55 and 1.57, P = 0.934), and the Nepean Dyspepsia Index (overall LSM change of -39.0 and -37.8, P = 0.537). Tegaserod was well tolerated. Diarrhea was the most common AE (8.1% tegaserod, 0% placebo). There were no serious AEs or deaths. CONCLUSIONS: A significant treatment effect was not demonstrated in this study using a treatment-withdrawal methodology. In future studies of functional dyspepsia patients with heartburn, a more rigorous parallel-group study design should be considered.