Integrated gastric acidity to evaluate acid suppression with PPI therapy: A five-way crossover comparison

656 patients with symptomatic GERD treated with pantoprazole 40 mg/day. The mean time to relief symptoms was 2 0 days for heartburn, 2.1 days for regurgitation, 2.2 days for dysphagia, and 2.1 days for chest pain Regarding SF-12 scale, we observed a significant improvement of the scores in the Physical component summary (Basal, week 8, week 24, week 48 : 43.9, 504, 51.6, 51.8 respectwely (p < 0.001)) and in the Mental component summary (Basal, week 8, week 24, week 48; 46.8, 50.8, 51.9, 51.9 respectively (p < 0.001)). The decrease observed in the GERD- HRQoL scale was significant (p
endoscopically healed at study end. Although low patient numbers must be taken into account, for patients suffering from erosive GERD grade C at baseline, a negligible higher percentage of patients in the pantoprazole group (67%) was healed compared to the esomeprazole group (45%), Conclusion: In patients with moderate to severe erosive GERD comparably high endoscopic healing and symptomatic relief were obtained with pantoprazole 40 mg and esomeprazole 40 rag, (Funded by ALTANA Pharma AG

$1615 Integrated Gastric Acidity to Evaluate Acid Suppression with PPI Therapy: A Five-Way Crossover Comparison Philip B. Miner Jr., Yusong Chen, Mark B. Sostek Introduction: Integrated gastric acidity (IGA) is a pharmacodynamic parameter that can document the absolute reduction in gastric acidity with acid inhibitory therapy over time. Effective treatments should reduce hydrogen ion concentration, thereby assunng adequate healing of erosive esopbagitis and symptom resolution. Unlike the commonly used parameter percent time pH >4.0, which measures only duration, IGA also takes into account the magnitude of clmnges in hydrogen ion concentration. Methods: IGA was calculated from standard nitragastnc 24-hour pH data collected at day 5 of dosing in a randomized, openlabel, comparative 5-way crossover study. H. pylori-negative patients aged between 18 and 60 years with symptoms of GERD received esomeprazole 40 mg, rabeprazole 20 rag, lansoprazole 30 rag, omeprazole 20 rag, or pantoprazole 40 mg qd for 5 consecutive momings 30 minutes prior to a standardized breakfast. There was a 10- to 17-day washout period between treatments, intragastric acidity (mmol.h/L) was measured with an intragastric pH probe, summed cumulatively per second and analyzed for each hour over a 24-hour period (as per Gardner et al, AmJ GastroenteroI 2001;96:1363). Results: The mean cumulative IGA for each of 5 proton pump inhibitors in the 34 evalnable patients on day 5 are shown (figure). Although this analysis was not designed to show a difference between comparators, the p-value between esomeprazole and all other comparators was <: 0.05 for a majority of the hourly time points (*). Conclusions: Esomeprazole provided significantly greater gastric acid suppression during most of a 24-hour time period than all other comparator PPIs as documented by lower levels of integrated gastric acidity.

$1613 Comparison of the Clinical Efficacy and Safety of Pantoprazole Vs Ranitidine Over Three Years to Prevent Relapse in Patients with Healed Erosive Esophagitis Joel Richter, Polly Fraga, Michael Mack, Andrew Dermovsesian, Susan Nielsen, Wieslaw Bocbenek, Wilfred Weinstein, The US GERD Pantoprazole Study Group, Abstract: Two identical, muhicenter, randomized, double-blind US studies compared 10-, 20-, and 40-rag once-dady (QD) doses of pantoprazole (PAN) and 150 mg of ranitidnie (RAN) trace daily (BID) in preventing relapse of erosive esophagitis (EE) in 721 patients enrolled with healing of EE documented by endoscopy. Helicobacter pylori was identified in 141 (20%) patients. Patients whose EE recurred within the first year were withdrawn from the study. After year 1, the)' were gwen 40 mg of PAN QD for 8 weeks. Healed patients resumed original treatment; treamrent failures were withdrawn. Methods: Endoscopy was peflbrmed at baseline and months l, 3, 6, 12, 24, and 36 or at discontinuation. Results: At 12 months, remission rates were significantly higher for PAN 40 mg (84% in one study and 81% in the other) than for RAN (32% and 33%). Healing was well maintained in patients remaining in the 40-rag group in years 2 and 3 (at least 84%). By the end of the studies (36 months), 79% of RAN patients had withdrawn (56% for lack of efficacy), compared with 47% (13% for lack of efticacy) for PAN 40 (p < 0.001; Table 1). Biopsies done at baseline and months 12, 24, and 36 revealed no significant differences in gastric atrophy, inflammation, or intestinal metaplasia among treatment groups from baseline through conclusion of the study. No adverse event had a significantly higher incidence in any PAN group compared with RAN. Withdrawals because of AEs showed no difference among groups. Conclusion: PAN 40 mg was well tolerated, maintained healing at a high rate over 3 years, and was superior to RAN 150 mg BID in healing maintenance at all lime points

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PAN 20 98 78 71 47 162 148 84 76 mg (66)*" (93)* (93) (26) *** PAN40 117 99 88 24 179 142 106 96 mg (82)*** (93)" (92) (13) *'* RAN 50 35 32 104 150 mg 185 154 (32) 46 (76) 37 (86) (56) BID a: (Denominators = patients in the risk set at the beginningof the year; intent-to-treatpatients who withdrew other than for relapse were excluded b: p-values are presented for PAN vs RAN: * =p<0.05, ** =p<0.01, ***=p<0.001

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S1616 Symptom and Esophageal Motor Response to Acid Infusion in the Esophagus Following 8 Weeks Treatment with Double Dose Proton Pump Inhibitor Therapy Vikas Bhalla, James Puckett, Jianmin Liu, Ravinder Mittal Background and Aims:Acid infusion into the esophagus induces heartburn (+ Bemstein test) and sustained esophageal contraction (SEC) in patients with reflux disease. An eight week course of Proton Pump Inhibitor (PPI) therapy relieves heartburn and heals esophagitis (endoscopically) in most patients. Our goal was to determine acid induced symptoms and motor events (SEC) in patients with a positive Bernstein test, prior to and 8 week after the treatment with double dose PPI therapy. Methods: Simultaneous manometric pressure recording and ultrasound imaging of the esophagus were performed in 11 Subjects with chronic heartburn during Bernstein test, before and after eight week treatment with Aciphex 20 mg bid. Two consecutive Bemstein tests were performed on the Pre PPI therapy and Post PPI therapy study days. Subjects scored onset and severity of heartburn/chest pain on a scale of 1-10. Data Analysis: Ultrasound images were digitized and analyzed every three seconds during the entire study penod, The muscularis propria (circular and longitudinal muscle) thickness was measured using computerized image analysis software. Results: PPI therapy relieved heartburn in all patients. However, Bernstein test became negative in only 1/ 11 patients. Acid infusion resulted in heartburn and an increase in the esophageal contraction amplitude and contraction duration. In addition, SECs were observed during acid infusion The latency, severity of heartburn and motor events during acid infusion were not affected by PPI therapy, Conclusion: Symptom resolution with PPI therapy does not correlate with resolution of acid infusion induced symptoms and esophageal contractile activity. A close correlation between heartburn and motility changes induced by acid infusion suggests a possible cause and effect between the two.

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Treatment With Pantoprazole 40 Mg And Esomeprazole 40 Mg Results In Comparable Healing In Patients With Erosive GERD LA Grade C Pichay Chueratanakom, Gudrun Gatz, Ursula Hole Aims: To compare pamoprazole 40 mg once daily (od) and esomepraaole 40 mg od in the treatment of patients wuh erosive GERD grades B/C (Los Angeles classification) with regard to endoscopically-proven healing and symptom relief. Methods: 227 patients with erosive GERD grades B (190) or C (37) were enrolled in this double-blind, muhicentre study and randomized either to the pantoprazole (N = 113) or esomeprazole (N = 114) treatment groups Both treatment groups were stratified to 1 of 3 different treatment durations with follow-up endoscopies at: a / 6 and 10 weeks, b) 4 and 6 weeks, or c) 4 and 8 weeks. If the patients were healed after the first period, the treatment was not continued and the second endoscopy not performed Overall healing rates were determined for the entire population and grouped by erosive GERD-grade at baseline. For each patient the results of the final study specific endoscopy were taken into account. At least equivalence of pantoprazole compared to esomeprazole was tested using Fisher's exact test. Symptom relief rates were determined as overall relief rates, as well. Significance of differences between pantoprazole and esomeprazole was determined by Fisher's exact test (two sided, significance level of 5%). Results: Overall, 95% of patients in the pantoprazole and 90% of patients in the esomeprazole group were healed (per protocol population). Analysis of these data showed an at least equivalence of the pantoprazole and esomeprazole regimens using a lower limit tor non-relevant inferiority of 5%. Relief from GERD-related symptoms was achieved in 54% and 51% of patients in the pantoprazole and esomeprazole group, respectively. In both treatment groups more than 90% of patients suffering from GERD grade B at baseline were

AGA Abstracts

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TABLE 1: REMISSION RATES IN PATIENTS WITH HEALED EE

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