Esomeprazole is effective as maintenance therapy in GERD patients with healed erosive esophagitis (EE)

A22 AGA ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

349 NOCTURNAL ACID BREAKTHROUGH - PREVALENCE & CLINICAL IMPLICATIONS. Andrzej Ukleja, Kenneth R. DeVault, Mark E. Stark. James S. Scolapio, Ronald A. Hinder, Diane M. Davis, Sami R. Achem, Mayo Clin, Jacksonville, FL. Recent studies indicate that nocturnal recovery of gastric acid secretion, termed "nocturnal acid breakthrough" (NAB), occurs despite treatment with twice daily proton pump inhibitors (PPI). This observation raises concerns about the therapeutic efficacy of PPI. Aims: I) Determine the prevalence of NAB at our center. 2) Compare the clinical and endoscopic findings of patients (pts) with and without NAB. 3) Evaluate whether pts with NAB have concomitant esophageal acid breakthrough (EAB). Methods: We reviewed the records of consecutive pts with GER on twice daily PPI referred for 24-hr pH testing. Data obtained included demographics, indications for the study, and endoscopy (EGD) findings. The pH tracings were analyzed for NAB (gastric pH ~4 lasting ;::,1 hour after nocturnal dose of PPI was taken) and concomitant EAB (esophageal pH ~4.0 lasting ;::,10 min.). In addition, the esophageal pH tracing was examined for the number of episodes and % time pH ~4 during the period of NAB. GER was diagnosed if 24-hr pH showed abnormal acid contact time (% time pH~4: upright ;::'8.1, supine ;::'3.4, and total ;::'5.5). Results: 23 pts (7M, 16F), mean age 62 (20-82), were referred for pH testing while taking PPI twice daily. All subjects took their PPI before meals except for one patient who consumed PPI at bedtime and was removed from the study. The remaining 22 pts are the subjects of this report. Indications for the study: persistent GER symptoms n=16 (73%), atypical GER n=6 (27%): chest pain n=3, cough n=3. See table for results. NAB was noted in all NAB( +) patients during the first 6 hrs after evening dose of PPI. Duration of NAB: mean 273 min (72-530). Conclusions: I) 64% of pts with GER-related symptoms taking twice daily PPI have NAB. 2) This phenomenon occurs in pts with typical and atypical GER symptoms. 3) The majority (96%) of pts on twice daily PPI have minimal or no esophagitis on EGD. 4) Concomitant EAB rarely occurs at the time of NAB. 5) Abnormal esophageal acid contact time was more common in pts with NAB than those without it. 6) The role of NAB in GER warrants further investigation.

Summary of Results Number Persistent Atypical of pts(%) GER GER NAB(+) NABH

14(64%) 8(36%)

EGO'

EGO'

EAB

(0·1)

(2,4)

(+)

Abnormal pH

nance treatment of healed EE and for resolution of heartburn. These results are consistent with results found in a parallel trial.

6-Month Maintained Healing Rate (Cumulative Life Table Rate, ITT Anaiysis)

Complete Healing Maintained (%) 95% CI(%) Mean Days to EERecurrence

E40 (n=92)

E20 (n=98)

E10 (n=91)

Placebo (n=94)

87.9' 804-954 130

7B.! 69.5-87B 101

542' 429-655 BO

29.1 176-406 46

'p<0.001 vsplacebo

351 H. PYLORI ERADICATION INCREASES THE INCIDENCE AND DURATION OF NOCTURNAL GASTRIC ACID BREAKTHROUGH PERIODS. Margot A. van Herwaarden, Melvin Samsom, Andre 1. Smout, Univ Med Ctr Utrecht, Utrecht, Netherlands. Nocturnal gastric acid breakthrough (NAB)occurs in up to 70% of the GERD patients treated with PPIs b.i.d. The effect of PPIs is decreased in the absence ofH. pylori (Hp). It is unknown whether Hp effects NAB. We aimed to investigate the effect of Hp eradication on NAB during PPI. Nineteen Hp-positive subjects were treated I week with 30 mg lansoprazole before breakfast, before and after Hp eradication. At the last day of both treatment periods with lansoprazole a 24-hour intragastric pH recording was performed using a glass-electrode. Before the start of the study and before the second treatment period HP status was assessed by testing antrum and corpus biopsy specimens by means of culture, histology, and rapid urease test. A 2-week placebo-controlled double-blind eradication therapy with ranitidine bismuth citrate 400 mg b.i.d. and c1arythromycin 500 mg b.i.d. was used. NAB was defined as intragastric pH<4 for more than I hour during the night. The number of subjects with NAB and the longest period with intragastric pH <4 during the night were determined. Statistical analysis was performed using Wilcoxon-rank test and Me Nemar test. Results: The table shows that the incidence of NAB and the duration of the longest period with intragastric pH<4 are increased after Hp eradication. Conclusion: Nocturnal acid breakthrough during PPI treatment occurs more often after eradication of H. pylori.

13

8 HP eradication before after

, Presence of esophagitis (Savary-Miller grade)

350 ESOMEPRAZOLE IS EFFECTIVE AS MAINTENANCE THERAPY IN GERD PATIENTS WITH HEALED EROSIVE ESOPHAGITIS (EE). Nimish B. Vakil, Reza Shaker, Clara Hwang, Donald D' Amico, Bernard Hamelin. Univ of Wisconsin Med Sch, Milwaukee, WI; Med ColI of Wisconsin. Milwaukee, WI; AstraZeneca LP, Wayne, PA. Objectives: To compare the efficacy of esomeprazole (an optical isomer of omeprazole) in doses of 40 mg (E40), 20 mg (E20). and 10 mg (EIO) once daily. with placebo (P) for the maintenance of healing of EE. Secondarily the effects of E40, E20, and E 10 on heartburn, safety, and tolerability were assessed. Methods: In this 6-month, US, multicenter, randomized, doubleblind, P-controlled trial, 375 patients who participated in an acute healing trial and had endoscopy-proven healed EE (LA Classification = "Not Present", H pylori-negative by histology) received E40 (n=92), E20 (n=98), EIO (n=91), or P (n=94). Endoscopy and symptom assessment were performed at baseline, and at I, 3, and 6 months after the start of maintenance therapy. Correlation between healing and symptom resolution was evaluated descriptively by visit. Mean time to EE recurrence was also evaluated. Results: Rates of maintained healing were significantly greater with esomeprazole compared with P (p
patients withNAB (n) longest period withgastric pH<4 during thenight(min)

4/10 38 (5-129)

10/10 1BO (146-237)

pvalue 0.03 0.005

sham eradication before after 5/9 66 (3-135)

4/9 35 (3-152)

p value

NS NS

data are presented asmedians (lOR)

352 ESOMEPRAZOLE (E) 40 MG PROVIDES MORE EFFECTIVE ACID CONTROL THAN PANTOPRAZOLE (P) 40 MG. Clive Wilder-Smith, Kerstin Rohss, Christina Lundin, Hans Rydholm, Gastroenterology Group Practice, Berne, Switzerland; AstraZeneca R&D Molndal, Molndal, Sweden. Introduction: E is the first PPI, developed as an optical isomer. The aim of this study was to compare the effect on intragastric pH of E 40 mg vs P 40 mg during single and repeated once daily oral dosing in patients with symptoms of GERD. Methods: In an open randomised, two-way cross-over study, 31 patients with symptoms of GERD (14 males; mean age: 28 yrs; mean weight: 67 kg) received E 40 mg or P 40 mg o.m. for 5 days with a wash-out period of at least 14 days between treatments. A 24-hr intragastric pH recording was performed on days I and 5 in each period. The percentage of time with intragastric pH>4 and pH> 3 during the 24-hr period and 24-hr median pH were analysed separately, using a mixed model ANOVA. The mean for each treatment and the mean treatment difference were estimated with 95% confidence intervals (CI). Results: See table below. No side effects attributable to E were noticed. Conclusion: E 40 mg provides significantly more effective acid control than P 40 mg. both after single and