Randomized Open-label Trial to Assess the Impact of Dosage Timing of Omeprazole/Sodium Bicarbonate (Zegerid 40 mg) on Healing of Severe Reflux Esophagitis: A Progress Report: 2010 Presidential Poster

Abstract

Purpose: Twice daily proton pump inhibitor (PPI) therapy is commonly recommended to heal severe reflux esophagitis. For optimal efficacy, patients are currently advised to take their PPI on an empty stomach 20 to 60 minutes before a meal - which can be a cumbersome process. Administration of a single nightly PPI regardless of meal time might increase adherence, and hence efficacy in healing esophagitis. Aim: To compare the efficacy of 8 weeks immediate-release omeprazole/sodium bicarbonate (IR-OME), taken either before breakfast or before bedtime, on healing severe esophagitis. Methods: Prospective open-label single-blinded cohort study of outpatients with LA Grade C or D reflux esophagitis randomized to IR-OME 40 mg taken 20 to 60 minutes before breakfast or before bedtime. Esophagogastroduodenoscopy (EGD) was performed at baseline and after 8 weeks of study medication. A 24-hour pH study was offered at the time of the follow-up EGD regardless of endoscopic findings. Results: To date, 88 subjects have been recruited of which 77 have completed the study [53 (69%) male, mean age 58 (SD 13, range 22 to 86), LA grades C=49, D=28]. Forty-one subjects were allocated to the morning dose and 47 to the bedtime dose (with 2 and 6 dropping out of each arm, respectively). Of 38 completed subjects (C=23, D=15) randomized to morning PPI, 32 (84%) had healed at 8 weeks. The 6 with persistent esophagitis all showed improvement in severity by one or two grades. Of 39 completed subjects (C=26, D=13) randomized to bedtime PPI, 33 (85%) healed. Four of 6 improved, one had the same grade, and one worsened in severity. 18 of 77 (23%) underwent pH testing while on study medication. Six discontinued study medication prior to pH probe placement and were excluded from subgroup analysis. Of the 12 subjects who underwent pH testing while on IR-OME (8 with standard probe, 4 with Bravo), 7 were on the morning dose of whom 6 (86%) showed normalization of their pH parameters. One subject on morning PPI demonstrated acid reflux (5.5% overall, 1.9% upright, 9.9% supine). Five subjects on bedtime PPI consented to pH testing; three (60%) with normalization of pH parameters. Amongst 4 subjects on morning vs. 4 on bedtime PPI each with gastric pH measurement obtained, there was no obvious difference for PPI effect on pH < 4 (mean 19.5, range 11.4-32% vs. 17.5, 0.2-52%). Conclusion: Both morning and bedtime dosing of IR-OME are highly and similarly effective in resolving severe LA grade C and D erosive reflux esophagitis at 8 weeks. Bedtime dosing was just as effective as morning dosing in controlling gastric acid production. Too few esophageal pH observations have been collected to comment on differences in nocturnal supine reflux between morning and bedtime dosing schedules. Disclosure: Dr Romero - Consultant: Santarus, and grant support for this project from Santarus. Dr Jung - won a travel award to attend DDW 2010 from Santarus. This research was supported by an industry grant from Santarus, Inc.