Once Daily Esomeprazole Versus Twice Daily Lansoprazole for GERD: a Double Blind Randomized Cross-Over Study

Purpose: Approximately 25% of patients taking first generation proton pump inhibitors (PPIs) are taking more than one per day. Previous pharmacodynamic studies have shown that this dosing strategy increases intragastric pH control to target >4.0 from approximately 12 to 16 hrs. Once daily esomeprazole has been previously shown to achieve intragastric pH control comparable to bid dosing of lansoprazole yet a clinical correlary of this observation has to date not been shown. Methods: The primary objective of this study was to evaluate esomeprazole once/day as non-inferior to continued bid lansoprazole using a computer randomized double blind cross-over design. Secondary objective was evaluation of ancillary medication use (antacids). Patients with typical and uncomplicated gastroesophageal reflux disease (GERD) who were well controlled on established bid dosing were recruited from a busy clinical gastroenterology practice. At entry, patients continued on blinded bid lansoprazole 30–60 min before breakfast and dinner or began esomeprazole 40 mg with a dummy placebo for the second dose. After 3 months, patients returned to baseline bid lansoprazole for 1 mo and then at month 4 crossed over to the second arm of randomization. Primary objective assessment was maintenance of normal range of GERD symptom score (HRQL score <11). All patients had baseline and exit endoscopy at entry and exit from the study. Results: 41 patients were screened but 6 “well controlled” patients did not have HRQL <11. A total of 35 patients were randomized 29 patients (18 M, 17 F) completed the trial: age- mean 59.1 ± SE 2.0 yrs, duration of lansoprazole bid use 19.5 ± 5 mo., BMI = 30.1 ± 0.6. All patient exits occurred in the first arm of randomization- reasons cited:exacerbation of symptoms (2 lansoprazole, 1 esomeprazole arm), nausea (1 lansoprazole), moved from area (1), exacerbation of preexisting coronary artery disease (1). There were no significant changes in BMI from entry to exit. The difference in HRQL scores (at 3 and 7 mo) was compared for each treatment arm compared to baseline with 2-tailed P-value is .1153 denoting non-significance. There was no difference in ancillary use of antacid use which was provided and usage tabulated at monthly study visits. No patient had evidence of erosive esophagitis at baseline or at month 7 exit from the study. Conclusion: 1. Patients with well controlled typical uncomplicated GERD on BID lansoprazole can have similar normalization of GERD HRQL with once daily esomeprazole. 2. This study confirms (with clinical implications) the pharmacodynamic data of comparable pH control for once daily esomeprazole compared to bid lansoprazole as previously reported.