Randomized Open-Label Trial to Assess the Impact of Dosage Timing of Omeprazole/Sodium Bicarbonate (Zegerid 40 mg) on Healing of Severe Reflux Esophagitis: Preliminary Results

Abstract

Purpose: Nighttime gastroesophageal reflux is important in the development of reflux esophagitis. For optimal efficacy, patients requiring proton pump inhibitor (PPI) therapy are advised to take their medication on an empty stomach 20 to 60 minutes before a meal which can be cumbersome. We hypothesized that immediate-release omeprazole/sodium bicarbonate (IR-OME), taken at bedtime, offers an alternative option for treatment of esophagitis. To test our hypothesis, we aimed to compare the percentage of subjects with severe esophagitis who achieve complete endoscopic resolution after 8 weeks of treatment with different dosage times: morning vs. bedtime. Methods: This is a prospective randomized open-label cohort study of outpatients with esophagitis. Subjects were educated about reflux disease and the proper technique and timing of the medication. Esophagogastroduodenos-copy (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. The goal is to treat 100 subjects (morning N=50, bedtime N=50). Results: To date, 58 subjects have been recruited of which 46 have completed the study [31 (67%) male, mean age 58 (SD 12.5, range 22 to 81), LA grades C=28, D=18]. Twenty-two subjects were allocated to the morning dose and 29 to the bedtime dose (with 1 and 4 dropping out of each arm, respectively). Of 21 subjects (C=10, D=11) randomized to morning IR-OME, 15 (71%) had healed at 8 weeks. The 6 with persistent esophagitis all demonstrated improvement in severity by one or two grades. Of 25 subjects (C=18, D=7) randomized to bedtime IR-OME, 19 (76%) healed (p=0.74). Four of 6 improved, one had the same grade, and one worsened in severity. Ten of 46 (22%) subjects accepted the offer to undergo pH testing while on study medication. Four discontinued the study medication prior to placement of the pH probe and were excluded from this subgroup analysis. Of the 6 subjects who underwent pH testing while on IR-OME, 5 were on the morning dose; 4 (80%) with normalization of pH parameters. One subject on morning IR-OME demonstrated acid reflux (5.5% overall, 1.9% upright, 9.9% supine). Only one subject on IR-OME at bedtime consented to pH testing; their time with acid in the esophagus was normal (0.8% overall, 1.6% upright, 0% supine). Conclusion: These preliminary results suggest that both morning and bedtime dosing of IR-OME are effective in resolving severe LA grades C and D erosive reflux esophagitis at 8 weeks. Too few pH observations have been collected to comment on differences in nocturnal supine reflux between morning and bedtime dosing schedules. Disclosure: Dr Alexander Consulting Meritigae Pharmacia and Wyeth; Research Funding - Merck, Novartis, and Glaxo Smith Kline. Dr Romero - Grant/Research Support and Consultant, Santarus, makers of omeprazole/sodium bicarbonate (Zegerid). No disclosures for: Drs Dawn Francis, Tushar Dabade, Adil Abdalla, Rayna Grothe, Vikneswaran Namasivayam, Kee Wook (Kevin) Jung, Michael Crowell, Felicity Enders, Amindra Arora, Joseph Murray, Steven Adamson, Ramona DeJesus, Andrew Majka, John Patt, Matthew Lohse, Judith McElhiney, Virender Sharma, Kaiser Lim, Ganapathy Prasad, or Angela O'Neil, or Mrs Debra Geno, Mary Fredericksen, or Nancy Diehl. Santarus provided study medication and financial support to conduct the study.