AGA Abstracts W1045 Efficacy of a New 175 Mg Bid Treatment By Racecadotril in Patients with Acute Diarrhea. Meta-Analysis of 2 Randomized Prospective Studies Benoit Coffin, Yoram Bouhnik, Philippe Baumer INTRODUCTION: Racecadotril, an enkephalinase inhibitor, shows pure intestinal antisecret- ory activity without antimotility action. This agent prolongs the antisecretory effect of endogenous enkephalins. Efficacy and tolerance of racecadotril 100 mg capsules (C100) given t.i.d in the symptomatic treatment of acute diarrhea has been previously established. As compared to the launched C100, an original 175 mg tablet formulation (T175), was shown to offer shorter Tmax, greater bioavailability and extended half-life in healthy volun- teers, suggesting its use as a b.i.d. antidiarrheal drug. AIMS & METHODS: We performed a meta-analysis was to assess the efficacy of T175 versus C100 in the symptomatic treatment of acute diarrhea in adults. Individual patient data (IPD) from all the existing studies were selected and those from all randomized patients having adequate research design were analyzed. The two randomized controlled trials were homogeneous as they have similar: a) studied endpoints - i.e the total number of diarrheic stools (NDS) and duration of diarrhea - treatment dosage, control treatment, b) inclusion criteria, sample size and duration of treatment. IPD meta-analytic tests were conducted by using a general Linear Mixed model where treatment effect was considered as random, and by adjusting on baseline severity. RESULTS: 456 patients were analyzed (the number of patients treated by C100 and T175 were respectively 111 and 110 in the first study, 118 and 117 in the second one). From an observed mean baseline NDS=5.96, T175 induced a highly significant reduction of NDS = -2.0 [-3.21, -0.78] (P<0.001) in comparison to the C100 group, increasing a 33 % relative efficacy of the treatment. The last diarrheic stool was observed 25% earlier in T175 group compared to the C100 group (P<0.02). By considering therapy success as patient recovery within the same day, we found a significant benefit of the T175 drug (OR=1.62 [10.7, 2.48]), with 10% more responder patients in the T175 group in comparison to C110, Number Needed to Treat NNT = 10 [5.43, 62]. CONCLUSION: This individual patient data meta-analysis demonstrates that the 175 mg tablet bid racecadotril formulation is significantly more efficient than the standard 100 mg capsule tid formulation. It suggests this new formulation is clinically relevant in patients with acute diarrhea, a frequent condition interfering with daily activities. W1046 Effect of a New Bid Treatment By Racecadrotil in Adult Patients with Acute Onset Diarrhea, a Non-Inferiority Study Benoit Coffin, Philippe Baumer INTRODUCTION: Racecadotril is a pure antisecretory drug developed in the treatment of acute diarrhea, in adults and children. Racecadotril acts as enkephalinase inhibitor that prolongs the antisecretory effect of endogenous enkephalins and has no antimotility action. Efficacy and tolerance of racecadotril 100 mg capsules (C100) given three times a day in the symptomatic treatment of acute diarrhea has been previously established. In comparison to the launched C100 formulation, a new 175 mg tablet formulation (T175) was shown to offer shorter Tmax, greater biovailability and extended half-life in healthy volunteers, sug- gesting its use as a b.i.d. antidiarrheal drug. AIMS & METHODS: The aim of this prospective randomized controlled double-blind, study was to assess the non inferiority of the T175 formulation as compared to C100 as a symptomatic treatment of acute diarrhea (less than 3 days of duration) in adult outpatients. The main criteria of judgement was the total number of diarrheic stools until recovery ; it was analysed by a covariance analysis. The secondary criteria of judgement was the actuarial duration of diarrhea, analysed by Kaplan-Meir and adjusted for baseline with comparison by log rank, then analysed by Cox proportional Hazard Survival. RESULTS: 221 patients (119 female, mean age : 40.8 yrs) have been included. As shown on table, the mean number of diarrheic stools was not inferior with T175 in comparison to C100. The duration of diarrhea was significantly shorter in the T175 group (13.7 hr) as compared to C100 (17.5 hr), Log Rank, P = 0.0238 (adjusted by baseline diarrheic severity). The Hazard Ratio was calculated : HR = 0.736 [95% CI=0.560 ; 0.968], P = 0.0283. Safety was good in both groups; adverse effects, never serious, were not different. CONCLUSION: This new formulation of racecadotril (175 mg tablet bid) was not inferior to the standard (100 mg capsule tid) administration of racecadotril; in addition it induced a shorter duration of diarrhea. * : least squared means are square-root transformed adjusted by baseline diarrheic severity † : P based on non-inferiority limit of 0.40 on square-root transformed data. A-622 AGA Abstracts W1047 Metronidazole-Furazolidone-or, Clarithromycine-Furazolidone-or, Clarithromycine-Based Regimen for Eradication of Helicobacter pylori in Peptic Ulcer Disease Saghi Riahizadeh, Shahram Agah, Nasrin Zendehdel, Reza Malekzadeh, Rasoul Sotoudehmanesh, Naser Ebrahimi-Dariani, Homayoun Vahedi, Morteza Khatibian, Javad Mikaeli, Akram Pourshams, Sadegh Massarrat Background: Furazolidone-based regimen has been effective against Helicobacter pylori in Iran, with no resistance, but with occurrence of side effects in the second week in few patients. Clarithromycine-based regimen is recommended as first line therapy in western countries. We compared the efficacy and side effect profiles of three anti H-pylori regimens. Methods: Patients with peptic ulcer disease verified by endoscopy and positive H-pylori infection were randomly allocated into three groups; group A received omeprazole 20 mg + amoxicillin 1g + bismuth subcitrate 240 mg twice daily each for 10 days combined with metronidazole 500mg for the first five days and Furazolidone 200mg for the second five days, twice daily(OAB-M5F5), group C received the same regimen but metronidazole was replaced by clarithromycine 500mg twice daily(OAB-C5F5); and group B received omepra- zole 20 mg + amoxicillin 1g + clarithromycine 500mg twice daily each for 10 days(OAC). H-pylori eradication was verified with 13C-urea breath test 8 weeks after the end of treatment. Results: Up to now, one hundred and sixty three patients (55, 58 and 50 in groups A-C) completed the study. Drug interruption was observed 1 in A and 1 in C. The most side effects complained by patients were bad taste, weakness as well as dry mouth. Dry mouth was with 66% more in B than in A and C(45%)(p<0.03).The per protocol eradication rate was 78, 79.4 and 70% in groups A-C respectively. Conclusion: 5 days Furazolidone-based therapy (A) with tolerable side effects seems to be effective as like as triple therapy with Clarithromycine (B). The end of our ongoing study will clarify the optimal regimen for the eradication of patients in Iran. W1048 Low Efficacy of PPI/AC Therapy for H. pylori-Eradication in Japan Takashi Kawai, Tetsuya Yamagishi, Kenji Yagi, Mikinori Kataoka, Kouhei Kawakami, Atsushi Sofuni, Takao Itoi, Yoshihiro Sakai, Fuminori Moriyasu, Yu Takagi, Tatsuya Aoki, Emiko Rimbara, Norihisa Noguchi, Masanori Sasatsu Background: Increase in CAM-resistant rate of H. pylori has been recognized in Japan. Resistance surveillance data from the Japanese Society for Helicobacter Research also show an increase from 18.9% in 2002 to 27.7% in 2004. The Maastricht 2005 Consensus Meeting Report recommends a PPI/AC regimen for initial H. pylori eradication therapy in regions where the incidence of CAM resistance is no more than 15-20%.We have investigated the usefulness of the regimens tailored for CAM-susceptibility using human feces. Method: 65 H. pylori positive patients were recruited. We divided the patients into two groups randomly. In one group, all patients received PPI/AC (lansoprazole (LPZ) 60mg + AMPC 1500mg + CAM 800mg 1wk) regimen regardless CAM-susceptibility before treatment (control group). In the other group, patients received PPI/AC regimen for CAM-sensitive (S), or PPI/AM regimen (LPZ 20mg + AMPC 1500mg + MNZ 500mg 1wk) for CAM resistance (R) with investigation into CAM-susceptibility before treatment (tailored group). The CAM susceptibil- ity test was conducted using patients feces by RFLP & nested PCR (Rimbara E, et al Curr Microbiol 2005; 51: 1-5). CYP2C19 phenotype status was also determined. Result: Eradication rates (ITT; intention to treat, 95% CI) were 84.8% (68-95) and 71.8% (53-86) in the tailored group and control group, respectively, with no significant difference. Moreover Eradication rates were 78.9% and 92.9% for the PPI/AC regimen for CAM-S and PPI/AM regimen for CAM-R in tailored group. On the other hand, Eradication rates were 84.2% and 53.9% for the PPI/AC regimen for CAM-S and CAM-R in control group. The eradication rates according to CYP2C19 phenotype were, for homoEM, hetEM and PM, respectively: 100% (4/4), 100% (3/3) and 75.0% (3/4) in PPI/AM, 100% (4/4), 71.4% (5/7) and 75.0% (6/8) for PPI/AC in tailored group. The eradication rates according to CYP2C19 phenotype were, for homoEM, hetEM and PM, respectively: 80.0% (4/5), 100% (6/6) and 80.0% (4/ 5) in PPI/AM, 50.0% (2/4), 66.7% (2/3) and 60.0% (3/5) for PPI/AC in control group. Conclusion: Tailored H. pylori-eradication therapy for CAM-susceptibility is very useful regimen in modern Japan where the CAM-resistance rate is high. PPI/AC therapy should not be conducted for H. pylori eradication in Japan now. W1049 Bismuth-Based Quadruple Therapy Is Effective in High Metronidazole Resistance Area Varocha Mahachai, Sombat Treeprasertsuk, Ratha-korn Vilaichone Metronidazole (MTZ) resistance is high in many geographical location and is not widely used in the H. pylori (Hp) triple regimen as a first line therapy. Resistance to commonly used clarithromycin ( C ), is increasing and has marked impact on eradication rate. C is not recommended in the area with resistance rate more than 15-20%. Thailand has high Hp infection rate more than 60% and is the area that MTZ-resistance is about 50% and C- resistance is about 20%. C-based triple regimen is a standard therapy commonly used for Hp infection. Overall eradication worldwide is approximately 75-80% due to antimicrobial resistance. In order to find the effective regimen in the area with high MTZ and C resistance, we conducted prospective study to determine eradication rate of bismuth-based quadruple therapy as a first line treatment for Hp infection. A total of 120 patients with active Hp infection identified by CLO-test® consisting of 114 NUD, 3 DU and 3 GU (mean age 43 yrs.) received 7 days of quadruple regimen (pantoprazole 40 mg bid, bismuth subsalicylate 1, 048 mg bid, amoxicillin 1 gm bid and MTZ 400 mg tid). 13C-UBT® was used to assess eradication after therapy. Gastric biopsy from each patient was obtained from antrum for C/S and E-test to assess antibiotic susceptibility. Minor adverse reactions such as nausea, metallic taste were found in 10% and none of the patients dropped out because of side effects. MTZ-resistance in these patients was 51.2%. Overall eradication rate was 83%.