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Heterogeneity among trials assessing effects of anti-secretory agentsin patients with endoscopic-negative reflux disease (ENRD): acritical overviewAjay Jain, MD1, Jia-Qing Huang, MD1 and Richard H Hunt, MD,FACG1*. 1Gastroenterology, McMaster University, Hamilton, Ontario,Canada.

Purpose: Although most patients with reflux disease have no endoscopicevidence of erosive esophagitis (EE) and are diagnosed as having ENRD,the current literature has focused primarily on the healing of EE. Patientswith ENRD are managed with H2-receptor antagonists and proton-pumpinhibitors (PPIs). However, comparison between studies has been difficultbecause of the lack of universally agreed definition of ENRD. The aim wasto identify sources of clinically important heterogeneity in studies assessingthe effects of H2RAs and PPIs in patients with ENRD.Methods: A medline search was conducted to March 2001 with keywords:“reflux, ENRD, NERD, cimetidine, famotidine, nizatidine, ranitidine, ome-prazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole”. Stud-ies included met the following criteria: (a) double-blind randomized trials(b) adult patients with heartburn, but without esophageal mucosal ero-sion(s) at endoscopy (c) patients treated with H2RAs and/or PPIs.Results: 1100 potentially relevant citations were identified, with 14 trialsmeeting the predefined criteria for this overview.

SOURCES OF HETEROGENEITYNO. OFTRIALS

Population1. Different definitions of ENRDa. Erythema, edema, friability of mucosa allowed 10b. Not clearly given 42. Patients on NSAIDS or Aspirina. Included 5b. Excluded 1c. Not given 8Outcome measurement and data presentation1. Only global symptom 32. Various specific symptoms (heartburn, regurgitation, pain, etc) 63. Complete relief of symptoms 64. Partial relief of symptoms 45. Percentage of symptom improvement 146. Change in symptom scores 8

Conclusions: The current literature on ENRD is chaotic making compar-ison between trials difficult. Varying definitions of ENRD, different end-points, outcome measurements and data presentation all contribute to thechaos of this literature. Consensus on the definition and strict criteria ofinvestigation are urgently needed for appropriate management of ENRD.

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Rabeprazole significantly improves health-related quality of life(HRQOL) in patients with symptoms of erosive gastroesophagealreflux disease (GERD)John Johanson, MD; Reshmi Siddique, PhD; Leonard Jokubaitis, MD;Ronald Hegedus, BA; Anita Murthy, PharmD; Anne Damiano, ScD;Ashoke Bhattacharjya, PhD University of Illinois, Rockford, Illinois.

Purpose: To assess the effect of rabeprazole 20 mg qd on HRQOL amongpatients with erosive GERD participating in the Future of Acid SuppressionTherapy (F.A.S.T.) trial, an open label, multicenter, 8-week study of theeffectiveness of rabeprazole.Methods: HRQOL was assessed at baseline and 8 weeks following treat-ment, using the SF-36TM Health Survey. Patients’ mean age was 52.1years; most were male (58.7%) Caucasians (85.7%).Results: Of the 2449 efficacy-evaluable patients in this study, 2428(99.1%) completed the SF-36 at the baseline study visit. Of the 1826patients with baseline and Week 8 clinical assessments, 1767 (96.8%)

completed the SF-36 at both visits. All SF-36 subscale and summary scalescores showed a statistically significant (p � 0.007) mean increase frombaseline to Week 8. Improvements in each of the 8 subscales exceptphysical functioning, general health, and mental health, were at least 5% inmagnitude. Furthermore, while baseline scores were significantly poorerthan general US population scores, follow-up scores for 4 of the subscales(role limitations due to physical problems, social functioning, role limita-tions due to emotional problems, and mental health) were commensuratewith the general population scores.Conclusion: Rabeprazole significantly improved HRQOL in patients withsymptoms of erosive GERD after 8 weeks of therapy, and restored socialfunctioning and emotonal well-being to levels commensurate with thoseobserved in the US general population.

Supported by: Eisai Inc., Teaneck, New Jersey, and Janssen ResearchFoundation, Titusville, New Jersey.

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Enteryx™ solution, a minimally invasive injectable treatment forGERD: initial multicenter human trial resultsDavid A Johnson, MD1*, James Aisenberg, MD2, Lawrence Cohen,MD2, Jacques Deviere, MD3, Raymond Foley, MD4, Robert Ganz, MD5,Gregory B Haber, MD6, Glen A Lehman, MD7, Jeffrey H Peters, MD8,David E Silverman, MD9 and Jill Visor9. 1Digestive and Liver DiseaseSpecialties, Norfolk, VA, United States; 2New York GastroenterologyAssociates, New York, NY, United States; 3ULB Erasme, Brussels,Belgium; 4Regional Gastroenterology Associates of Lancaster,Lancaster, PA, United States; 5Minnesota Clinical Research Center,Minneapolis, MN, United States; 6St. Michael’s Hospital, Toronto,Canada; 7Indiana University Medical Center, Indianapolis, IN, UnitedStates; 8University of Southern California, Los Angeles, CA, UnitedStates; and 9Enteric Medical Technology, Foster City, CA, UnitedStates.

Purpose: Recently there has been intense interest in developing endoscopicmethods to improve competency of the lower esophageal sphincter (LES)to treat patients with gastroesophageal reflux disease (GERD). Enteryx isan inert biocompatible ethylene vinyl alcohol polymer, which is injectedendoscopically into the muscular layer of the LES during an outpatientprocedure. Enteryx is designed to increase the basal pressure and reduce thedistensibility of the LES (preventing inappropriate relaxations leading toreflux events). Preliminary data from 15 patients in a European pilot studyshowed that implantation of 3–6 mL (Enteryx) at the LES improved GERDparameters in 13/15 PPI dependent GERD patients.Methods: Recruitment has been completed for a multicenter European/North American protocol (n � 75). Inclusion criteria: 1) GERD symptomscontrolled with PPI 2) 24 hour pH with � 5% time with pH �4; 3)Velanovich GERD score � 11 on PPI and � 20 off PPI. Exclusion criteria:1) Erosive esophagitis � grade 3 2) Hiatal hernia � 3 cm 3) Barrett’sesophagus 4) Esophageal body motility disorder 5) Varices 6) Body massindex �35. Procedure: Enteryx was injected via a 4mm sclerotherapyneedle into the deep submucosal/muscular levels of the LES/cardia. Flu-oroscopy was used to confirm intramuscular injection. Per protocol, GERDparameters will be followed for 1 year while off PPIs.Results: Data was analyzed for 1, 3 and 6 months. At 1 month, symptomscores improved by an average of 64% (n � 35) with 32 patients off allPPI/H2 antagonist medication and 3 patients taking PPIs on demand. At 3months, symptom scores improved by an average of 83% (n � 21), with 18patients off all PPI/H2 antagonist medication and 3 patients taking PPIs ondemand. Initial 6 month (n � 9) data shows improvement in symptomscores (82% average improvement) and medication use (7 patients off allsystemic GERD medications), with a normalization in 24 hour pH score in4/6 patients submitting for testing. No clinically significant complicationshave been associated with the procedure, although most patients reportretrosternal pain for 1–7 days following the procedure.

S17AJG – September, Suppl., 2001 Abstracts