Esomeprazole 40 mg provides more effective acid control than lansoprazole 30 mg

A20 AGA ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

341

343

CISAPRIDE, CIMETIDINE, BOTH, OR NEITHER FOR INFANTILE ESOPHAGITIS: SYMPTOMATIC & HISTOLOGIC RE· SUL TS OF 2-MONTHS RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED THERAPY IN 100 BABIES. Susan R. Orenstein, Theresa M. Shalaby, Eric A. Frankel, Sherry F. Kelsey, Acad Hosp of Pittsburgh & Univ of Pittsburgh, Pittsburgh, PA; Acad Hosp of Pittsburgh, Pittsburgh, PA; Univ of Pittsburgh Sch of Medicine, Pittsburgh, PA; Univ of Pittsburgh, Pittsburgh, PA.

ESOMEPRAZOLE IS SUPERIOR TO OMEPRAZOLE FOR THE HEALING OF EROSIVE ESOPHAGITIS (EE) IN GERD PATIENTS. Joel E. Richter, Peter J. Kahrilas, Clara Hwang, Yictoria Marino, Bernard Hamelin, Cleveland Clin Fdn, Cleveland, OH; Northwestern Univ, Chicago, IL; AstraZeneca LP, Wayne, PA. Background: Until now, no randomized, controlled trials have shown any PPI to be superior to omeprazole in healing across all grades of EE. Pharmacologic studies with esomeprazole, an optical isomer of omeprazole, have demonstrated potential for clinical benefit of this new PPJ. Methods: This double-blind, randomized trial, was conducted at 163 centers in the US. 2425 H pylori-negative (by serology) patients with photodocumented EE (LA Classification grades A-D) received esomeprazole 40 mg (E, n=1216) or omeprazole 20 mg (0, n= 1209) qd for up to 8 wks. The primary efficacy variable was the proportion of patients healed at wk 8. Secondary variables were the proportion of patients healed at wk 4, resolution of heartburn and regurgitation, time to sustained heartburn resolution (7 consecutive days without heartburn), and proportion of days and nights without heartburn. Tolerability was also evaluated. Results: E resulted in significantly greater healing of EE at 4 and 8 wks (table) across all grades. E was significantly more effective than 0 for all symptom variables. The proportion of patients with treatment-related adverse events was comparable for E and 0 (15.3% and 15.1%, respectively). Conclusions: Esomeprazole had a similar healing rate at wk 4 as omeprazole had at wk 8. Esomperazole is the first PPI to demonstrate significant clinical advantages over omeprazole in healing across all grades of EE and symptom resolution. These results are consistent with the results of an earlier trial.

To determine optimal therapy of infantile esophagitis, we studied 100 babies prospectively for Iy, with symptomatic (Sx)and histologic (Bx) re-evaluation every 2mo for 6mo, and again at 12mo. We present 2-mo results using intention-to-treat analysis for the 96 enrolled >2mo by 1211/99. METHODS: Between 7/1/94 & 10113/99, 736 babies were screened, 473 met inclusion criteria, 208 consented to blind esophageal suction biopsy', 180 (87%) had esophagitis, 100 consented to study. Treatment assignment was randomized, double-blind in blocks of 8 to cisapride/placebo (cis), cimetidine/placebo (cim), cisapride/cimetidine (both), or dual placebo (neither). Dosing was cis 0.2mglkg qid, cim IOmglkg qid. Outcome measurements were Sx (Infant Gastroesophageal Reflux Questionnaire, 1992b ) and Bx (papillary height (P) & basal layer thickness (B) via eyepiece micrometer). Babies who were changed per protocol to both because of failure of therapy (cis, 2; cim, 2; both,2; neither, I) and those who failed follow-up (cis, I; cim, 4; both,2; neither, 4) were considered "Worse" for purposes of analysis, and combined with those deemed "Worse" by their parent. Analysis for differences by Chisquare; significance p<'IO. RESULTS: Sx: Babies treated with cisapride (cis or both) were more likely to be deemed overall "Well" or "Better" (86%), vs. "Same" or "Worse", after 2mo therapy than infants treated without cisapride (cim or neither, 70%). Vomiting: The overall improvement in reflux symptoms was not accompanied by a statistically significant improvement in vomiting frequency or volume. Crying: Although most babies improved or stayed the same in daily duration of crying, some babies on each therapy except cis had more daily crying after 2mo therapy. Bx: Regardless of treatment group, B was more likely to improve in 2mo (65%) than was P (45%), p<0.2. Basal layer was improved in more babies by cim (78%) than by cis or neither (62%), but did not reach significance. CONCLUSIONS: A regimen with cisapride in it was more likely to result in clinical improvement at 2mo than one without cisapride in it, although the symptomatic and histologic correlates of this improvement are incompletely defined. REFS: a. Putnam PE. Gastro 1992;102:AI49. b.Orenstein SR. Clin Pediatr 1993; 32:472. c. Black DO. Gastro 1990; 98:1408.

EE Healing and Symptom Resolution (Cumulative Life Table Rate, ITT Analysis) Esomeprazole (n=1216)

Omeprazole (n=1209)

p value

93.7% 817%

84.2% 68.7%

<0.001 <0.001

68.3%

58.1%

<0.001

80.1%

75.2%

0003

5 749 ± 29.8 90.8 ± 16.9

8 69.7 ± 30.5 87.9 ± 18.8

<0.001 <0.001 <0.001

Week 8 Healing (%) Week 4 Healing (%) Investigator Assessment of Heartburn Resolution (week 4) Investigator Assessment of Resolution of (week 4) Regurgitation Time to Sustained Resolution of Heartburn (Median # of days) % Days WIthout Heartburn (mean ± SO) % Nights Without Heartburn (mean ± SO)

342 THE EFFECT OF CISAPRIDE AND STIMULATED SALIVATION ON ESOPHAGEAL ACID CLEARANCE IN OLDER ADULTS. William C. Orr, Sheldon Sloan, Lynn Institute for Healthcare Research, Oklahoma City, OK; Dept of Med Affairs, Janssen Pharmaceutica, Titusville, NJ. Salivation is known to play an important role in the clearance of refluxed acidic gastric contents. Studies have shown that inhibiting salivation will markedly prolong the acid clearance process. As a cholinergic drug, cisapride appears to promote salivation, but the exact nature of its role in the acid clearance process remains to be elucidated. We chose to study a population of older symptomatic adults since reflux problems appear to increase with age and older adults do have a higher frequency of swallowing disorders. The aim of the present study was to compare in a population of older adults the effects of cisapride to stimulated salivation on the number of swallows required to neutralize l5cc of 0.1 NHcl infused into the distal esophagus. SUBJECTS: Subjects were 15 older adults ranging in age from 65 to 84 with a mean age of 72.2 yrs. All individuals had symptoms of heartburn at least four times a week with antacid consumption at least once a week. All subjects had an esophageal motility evaluation to rule out the presence of a primary esophageal motor disorder. Esophageal pH was measured 5cm above the manometrically determined proximal border of the lower esophageal sphincter. The basic acid clearance process involved the installation of 15ml of 0.1 NHcl in to the distal esophagus. The patient was required to swallow every 30 seconds, and the number of swallows required to produce an esophageal pH above 4.0 for 30 seconds was determined. This process was accomplished under normal conditions and while allowing a peppermint lozenge to dissolve in the mouth. These two conditions were repeated under a baseline condition and subsequent to one week of treatment with cisapride, 10mg, qid. RESULTS: The condition of the lozenge alone resulted in a significant decrease in the number of swallows required for acid clearance (mean = 9.8 vs 6.4, p < .01). Cisapride alone also produced a significant decrease in the number of swallows to acid clearance (10.2 vs 7.0, P < .05). There was no difference between the number of swallows to clear comparing the lozenge condition without cisapride and cisapride alone (6.4 vs 7.0 respectively). CONCLUSIONS: I) Acid clearance with cisapride is comparable to acid clearance under normal conditions with salivary stimulation. 2) In addition to its prokinetic effects, another important mechanism through which cisapride acts to relieve heartburn and enhance healing of esophagitis appears to be through the stimulation of salivary flow.

344 ESOMEPRAZOLE 40 MG PROVIDES MORE EFFECTIVE ACID CONTROL THAN LANSOPRAZOLE 30 MG. Kerstin Rohss, Catharina Claar-Nilsson, Hans Rydholm, Lars Nyman, Astrazeneca R&D Molndal, Molndal, Sweden; Quintiles AB, Uppsala, Sweden. Introduction: Esomeprazole is the first PPI, developed as an optic isomer, to be available for clinical use. It has higher oral bioavailibility, resulting in greater acid suppression compared to omeprazole. The aim of this study was to compare the effect on intragastric pH of esomeprazole 40 mg versus lansoprazole 30 mg during repeated once daily oral dosing in healthy male and female subjects. Methods: In an open randomised, two-way cross-over study, 20 healthy male and female subjects (15 males; mean age: 27 years; mean weight: 72 kg) received esomeprazole 40 mg or lansoprazole 30 mg once in the morning for 5 days with a wash-out period of at least 14 days. A 24-hour intragastric pH recording was performed on day 5 in each peroid. The percentage of time with intragastric pH>4 and percentage of time with pH> 3 during the 24-hour period and 24-hour median pH were analysed separately, using a mixed model analysis of variance (ANOYA) with fixed effects for period, sequence and treatment and a random effect for subject within sequence. 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 esorneprazole were noticed. Conclusion: Esomeprazole 40 mg provides significantly more effective acid control than lansoprazole 30 mg, suggesting a potential for improved clinical efficacy in the treatment of acid related diseases.

% of 24-hr withpH>4' _'/,of 24-hr w~h pH>3' 24·hour median pH % of subj. with pH>4for>12 hr % of sub]. with pH>4 for >16 hr

'Mean (95%CI)

Esomeprazole (A)

Lansoprazole

65.4 (59.5-71.3) 768 (71.4-82.2) 4.8 (4.5-5.1) 90

53.5 (47.0-58.9) 675 (62.1.72.9) 42 (3.9·45) 57

38

A·B

p·value

12.4 (7.4-17.5) 9.3 (4.9-13.7) 06 (03-09)

<0001

(8)

<0001 <0.001