An Exploratory Open Label Trial of Tegaserod in Non-Erosive GERD Patients with Incomplete Response to PPIʼs

Abstract

Purpose: Forty to 50% of patients treated with PPI's for non-erosive GERD (NERD) have persistent upper gastrointestinal symptoms. A previous study has shown that tegaserod improves variables of mechanical hypersensitivity and symptoms in patients with functional heartburn, suggesting tegaserod may be useful in symptomatic NERD. Aim: To determine if addition of tegaserod (6mg BID) to a prescribed PPI regimen improves: (1) Global GERD assessments and (2) occurrence, frequency, severity and distress of 10 upper gastrointestinal symptoms. Methods: This 4-week open-label, randomized, two-center, parallel-group pilot study followed a 4-week screening and 2-week baseline period. NERD patients on stable PPI's for at least 30 days with persistent symptoms were eligible. Treatments were: PPI + tegaserod 6 mg bid (Teg) or PPI alone in a 2:1 allocation. Patients completed weekly and end of treatment global symptom assessments. A GERD Symptom Assessment Questionnaire (GSAQ) was completed at screening and after treatment. A Global Composite Index Score (GCIS) was calculated from the GSAQ. Within-treatment changes from baseline were evaluated using paired t-tests. Between treatment comparisons employed analyses of covariance for continuous parameters, van Elteren's test for ordinal parameters, and Cochran-Mantel-Haenszel tests for dichotomous parameters. Results: Forty-one patients were evaluated (Age 21–63 yrs; 20 Males, 21 Females; n = 27 Teg + PPI; n = 14 PPI). Between treatment comparisons of global GERD assessments vs. pre-study were significant for Teg + PPI at week 1 (p = 0.02) and week 3 (p = 0.03). Occurrence of heartburn/acid reflux, regurgitation, abdominal bloating and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Frequency, severity and bothersomeness of regurgitation and nausea were improved at the final visit by Teg + PPI vs PPI alone (all p < 0.05). Teg+ PPI improved the GCIS from baseline to the final visit (p = 0.0002). Tegaserod was well tolerated, with no serious adverse events reported. Conclusions: Tegaserod in combination with a PPI significantly improved several global and individual symptom assessments in NERD patients with incomplete relief from PPI's. Data from this trial justifies investigation of the potential utility of tegaserod in patients with NERD.