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Efficacy and Safety of Vonoprazan-Based Triple Eradication Therapy for Helicobacter Pylori Infection in 890 Patients
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POLAPREZINC COMBINED WITH TRIPLE THERAPY FOR HELICOBACTER PYLORI ASSOCIATED GASTRITIS: A PROSPECTIVE, MULTICENTER, RANDOMIZED CLINICAL TRIAL Bei Tan, Hanqing Luo, Hong Xu, Nonghua Lu, Ruihua Shi, Hesheng Luo, Jiansheng Li, Jian-Lin Ren, Yiyou Zou, Yanqing Li, Feng Ji, Jing-Yuan Fang, Jiaming QIan
COMPARISON OF AOC AND AOM TRIPLE, SEQUENTIAL, AND CONCOMITANT THERAPY AS THE FIRST LINE ERADICATION THERAPY FOR HELICOBACTER PYLORI Jin Il Kim Background/Aim: The eradication rates of the AOC standard triple therapy have continuously decreased, because of the widespread development of clarithromycin resistance. We compared the efficacy and adverse events of standard triple, sequential, and concomitant therapy for H. pylori eradication. Method: This was a prospective, multicenter, randomized controlled study involving 1,000 patients diagnosed with H. pylori infection between January 2014 and July 2016 in the five Catholic University Hospitals in affiliation. Diagnosis was made by histological evidence of H. pylori via Warthin-Starry silver staining. We compared 4 treatment regimens and 250 patients were enrolled in each group: the AOC therapy was treated with clarithromycin based triple therapy for 7 days; the AOM therapy was treated with metronidazole based triple therapy for 7 days; the sequential therapy consisted of rabeprazole and amoxicillin for the initial 5 days, followed by rabeprazole, clarithromycin, and metronidazole for the subsequent 5 days; the concomitant therapy consisted of rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. Six weeks following completion of therapy, successful H. pylori eradication was defined by a negative 13C-urea breath test result. Adverse events and drug compliance were evaluated by physicians via direct questioning. Results: A total of 896 patients (224, 223, 218, and 231 patients in the concomitant, sequential, AOM Triple, and AOC standard triple groups, respectively) were analyzed. The mean age of the patients was 55.7 years. There were 464 male and 432 female patients. The eradication rate was significantly higher in the concomitant group (89.7%, 204/224) than in the AOC standard group (78.3%, 181/231), the AOM group (82.6%, 180/218) and the sequential group (85.7%, 191/223) (p=0.006). Drug compliance and adverse events were not statistically different among the three groups. Conclusions: Concomitant therapy appears to be more effective for H. pylori eradication compared to AOC, AOM triple therapy and sequential therapy. There were no statistically different adverse events among the three groups.
Background: Helicobacter pylori is one of the most prevalent global pathogens and treatment failure is increasing due to rising antibiotic resistance. Polaprezinc is a gastric mucosal protective agent complex of zinc and L-carnosine, shown to improve efficacy when combined with triple therapy in Japan. Aim: To compare the clinical efficacy and safety of the polaprezinc combined to triple therapy versus standard triple therapy in the eradication of H. pylori. Methods: This is a randomized, parallel-group controlled, prospective multicenter study in 11 cities of China. Treatment-naïve patients with H. pylori-associated gastritis were randomly assigned to the following groups: Arm A which consists of triple-therapy (omeprazole 20mg, amoxicillin 1g, and clarithromycin 500mg twice daily) plus polaprezinc 75mg twice daily, Arm B which consists of the same triple-therapy plus polaprezinc 150mg twice daily, or Arm C which is the standard triple-therapy for 14 days. Eradication was considered successful if C13 or C14 urea breath test was negative 4 weeks after completion of therapy as the primary outcome. Digestive symptoms improvement 7, 14, 28 days after completion of intervention and rates of adverse effects were the secondary outcomes. Results: 332 enrolled, and 303 patients completed the study, with 106, 96, and 101 patients in Arm A, Arm B, and Arm C. In the intention-to-treat (ITT) analysis, the rate of H. pylori eradication was significantly higher for Arm A (77.0%) and Arm B (75.9%) vs Arm C (58.6%) (p<0.01), whereas there was no difference between Arm A and Arm B (P=0.90) (Table 1, Figure 1). In the per-protocol (PP) analysis, the rate of H. pylori eradication was significantly higher for Arm A (81.1%) and Arm B (83.3%) vs Arm C (61.4%) (P<0.01), while there was no difference between Arm A and Arm B (P=0.62) (Table 1, Figure 1). In all three groups, there were significant symptomatic improvement including abdominal pain, acid reflux, belching, heartburn, bloating, nausea, and vomiting at 7 days, 14 days and 28 days after treatment compared to baseline (P<0.0001). The adverse event rate of Arm B was higher than Arm A (P=0.04) and Arm C (P=0.02), including mild leukopenia, elevated liver enzymes, elevated serum uric acid, and high blood pressure, but there were no serious adverse events. Conclusions: Standard dose polaprezinc combined with standard triple therapy can significantly improve H. pylori eradication rate without an increase in adverse event and is well-tolerated. H. pylori eradication rate in the ITT and PP populations
Sa1197 THE EFFICACY OF PCR-BASED TAILORED ERADICATION THERAPY FOR IN-PATIENTS WITH HELICOBACTER PYLORI INFECTION Young Sin Cho, Su Jung Han, Il-Kwun Chung, Yunho Jung, Tae Hoon Lee, Sang-Heum Park, Sun-Joo Kim Background/Aims: Helicobacter pylori (HP) is the causative pathogen of gastrointestinal diseases such as peptic ulcers and gastric malignancy. The eradication rates of HP infection are decreasing because of increasing resistance to clarithromycin. A previous study showed that a polymerase chain reaction (PCR)-based assay can detect HP and clarithromycin resistance. The aim of this work was to compare the efficacy of PCR-based tailored therapy with that of conventional triple therapy. Methods: From April 2015 to August 2016, 285 consecutive HP-infected patients received PCR-based tailored therapy or standard triple therapy (proton pump inhibitor, clarithromycin, amoxicillin) for 10 days. In the PCR-based tailored therapy group, patients received standard triple therapy or quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) according to clarithromycin resistance confirmed by the PCR-based clarithromycin resistance test, which detects most of the prevalent point mutations (A2143G and A2142G) in HP 23S rRNA. Eradication was assessed using the 13C-urea breath test 6-8 weeks after treatment. Eradication rates and adverse drug effects were compared between groups. Results: The mean age of the patients was 55.5 years. Standard triple therapy was administered to 191 patients and PCR-based tailored therapy to 94 patients. The eradication rates of standard triple therapy and PCR-based tailored therapy were 64.3% (126/191) and 84% (79/94) by intention to treat analysis, respectively (P = 0.005), and 72.4% (126/174) and 88.8% (79/89) by per protocol analysis, respectively (P = 0.002). The complication rates of the PCR-based tailored therapy and standard triple therapy groups were similar (11.1% vs. 12.4%, p=0.629). Conclusions: In HP-infected patients, PCR-based tailored therapy is more effective than conventional triple therapy and can substitute as the first-line HP eradication regimen in regions with high rates of clarithromycin resistance.
ITT, Intention-to-treat; PP, per-protocol; Arm A, polaprezinc 150mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm B, polaprezinc 300mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm C, omeprazole, amoxicillin and clarithromycin for 14 days.
Sa1198 EFFICACY AND SAFETY OF VONOPRAZAN-BASED TRIPLE ERADICATION THERAPY FOR HELICOBACTER PYLORI INFECTION IN 890 PATIENTS Taro Akashi, Daisuke Fukuda, Yutaka Fukuda, Yuko Akazawa, Kazuhiko Nakao Background and aim: Helicobacter pylori infection is the most common infectious disease worldwide, and is a cause of gastric cancer. The first line therapy for H. pylori infection has comprised co-administration of a proton-pump inhibitor (PPI) with two antibiotics, typically, amoxicillin and clarithromycin in Japan. However, with conventional PPIs, 3-5 days are required for lowering intragastric pH to the optimal levels for H.pylori eradication. Vonoprazan, a potassium-competitive acid blocker which rapidly and efficiently inhibits acid secretion, was approved in Japan in 2015. Information regarding Vonoprazan-based H.pylori eradication is still limited. In this study, we investigated the efficacy and tolerability of vonoprazanbased triple eradication therapy for H. pylori infection. Methods: This study included 890 patients (938 cases) who received vonoprazan-based triple eradication therapy for H. pylori infection in a single center. Eight hundred twenty five patients received first line therapy for H. pylori infection with vonoprazan, clarithromycin, and amoxicillin for seven days. One hundred thirteen patients, who had failed first line therapy at our center or other institutions, received second line therapy with vonoprazan, metronidazole and amoxicillin for seven days. Eradication of H. pylori was confirmed by urea breath test in all patients at least a month after the treatment. Eradication rate and side effects were then analyzed. Results: The patients consisted of 510 male (mean age: 58.5±11.3) and 380 female (mean age: 60±11.2). Among the 825 patients who received the first line therapy, H. pylori eradication was achieved in 759 patients (92.0%). Among 113 patients who received the second line
Figure 1 H. pylori eradication rate in the ITT and PP populations ITT, Intention-totreat; PP, per-protocol; Arm A, polaprezinc 150mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm B, polaprezinc 300mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm C, omeprazole, amoxicillin and clarithromycin for 14 days.* p<0.01
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therapy, H. pylori eradication was achieved in 112 patients (99.1%). The overall rate of grade 2 side effects was 2.9%. The side effects included nausea and diarrhea (1.01%), abdominal pain (0.67%), skin rash (0.67%), heartburn (0.56%), vomiting (0.22%), and constipation (0.22%). There was no distinct difference in rate of side effects between first line therapy and second line therapy. Eradication rate was not significantly different between age groups (<65, 65-74, >74 years) or genders. Conclusions: Our data demonstrate that vonoprazan-based triple therapy is an effective and relatively safe treatment for H. pylori infection.
Sa1201 A MULTICENTER, OPEN-LABEL, RANDOMIZED TRIAL OF VONOPRAZAN VERSUS PPI BASED 7-DAY TRIPLE THERAPY FOR THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION Soichiro Sue, Hirohumi Kuwashima, Isao Arima, Marina Ogushi, Satoshi Nakao, Makoto Naito, Kazuto Komatu, Hiroaki Yamada, Hiroaki Kaneko, Toshihide Tamura, Tomohiko Sasaki, Masaaki Kondo, Wataru Shibata, Shin Maeda Background Vonoprazan is a novel potassium-competitive acid blocker and eradication rate (ER) of vonoprazan (V)-based first line triple therapy with clarithromycin (C) and amoxicillin (A) (VAC) was reported to be 97.6% in patients infected with clarithromycin-susceptible strains in the phaseIII trial. On the other hand, our real-world prospective multi-center cohort study showed under 90% ER for CAM-susceptible (CAM-S) strains (DDW2016, Tu1347). Thus, the aim of this study was to validate the ERs of VAC by multicenter, prospective randomized trial. Method One hundred sixty (160) H. pylori positive by culture test, treatment naïve, patients form 3 hospitals were included. MICs of CAM were determined by agar-dilution methods and the patients were divided into three groups: 41 of CAMresistant (CAM-R) H. pylori, 106 of CAM-S H. pylori and 13 of failure for determination of agar dilution test. CAM-S group were randomized (minimization method with age and sex) to VAC or PAC ; P (lansoprazole 30mg b.i.d., rabeprazole 10mg b.i.d. or esomeprazole 20mg b.i.d.), A (750mg b.i.d.), C (200mg or 400mg b.i.d.). All CAM-R group were eradicated with VAC; V (20mg b.i.d.), A (750mg b.i.d.), C (200mg or 400mg b.i.d.). Average 7.6 weeks after therapy (at least 4weeks) eradication was determined by 13C urea breath test. Safety was evaluated by side effects questionnaire (SEQ) filled by patients during therapy as previously descried. Results Two arms had similar patients demographics (VAC: Female 32%, Age 64±12, PAC: Female 31%, Age 62±13) and no significant differences in clinical background (smoking rate, CAM dose and endoscopic finding). Per-protocol analysis demonstrated no differences between ER of VAC and PAC in CAM-S group (88.9% vs 86.7%, respectively, difference: 2.2%; 95% confidence interval, -10.8%-15.2%). ER of VAC in CAMR group was 82.9%. No significant differences of SEQ score between VAC and PAC were observed: diarrhea, dysgeusia, nausea, anorexia, abdominal pain, heartburn, hives, headache, abdominal fullness, belch, vomiting, and general malaise. Conclusion In the current RCT, we confirmed VAC ER was less than 90% and similar to PAC in patients with CAM-S strains. VAC ER in the patients with CAM-R strains was 82.9% and similar to the phaseIII result (82.0%). These results suggest vonoprazan-based regimen should be applied for the patients in the countries and regions with high frequency of CAM-R strains. Trial registration number UMIN000016337
Sa1199 EFFECTIVENESS OF 7-DAY AND 14-DAY MOXIFLOXACINDEXLANSOPRAZOLE BASED TRIPLE THERAPY AND PROBIOTIC SUPPLEMENT FOR HELICOBACTER PYLORI ERADICATION IN THAI PATIENTS WITH NON-ULCER DYSPEPSIA: A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED STUDY Peranart Chotivitayatarakorn, Sith Siramolpiwat, Soonthorn Chonprasertsuk, Amornnivit Kanokwanvimol, Anupong Tangaroonsanti, Patommatat Bhanthumkomol, Bubpha Pornthisarn, Varocha Mahachai, Ratha-Korn Vilaichone Background: H. pylori is important risk for gastric cancer. Moxifloxacin is used for second line but limited studies as first line therapy. Probiotics might decrease side effects and improve eradication rate but remain uncertain. This study was designed to evaluate efficacy of moxifloxacin-dexlansoprazole based triple therapy with probiotic for first line H. pylori eradication in Thailand. Methods: H. pylori gastritis patients were randomized to receive 7-or14-day regimen with probiotic or placebo. Treatment regimen comprises dexlansoprazole(60mg) twice daily, moxifloxacin(400mg) once daily and clarithromycin MR(1g) once daily. Probiotic was Saccharomyces boulardii in capsule(282.5) prescribed twice daily. CYP2C19 and cagA genotypes along with antibiotic tests were performed. Eradication was defined as negative 13C-UBT 4 weeks after treatment. Results: 112 subjects were enrolled(28 each to 7-and 14-day regimens with probiotic or placebo). Antibiotic tests demonstrated 29% fluoroquinolone, 19% metronidazole and 4% clarithromycin resistances. CYP2C19 genotype revealed 39% rapid metabolizer(RM), 46% intermediate metabolozer(IM) and 10% poor metabolizer(PM). CagA genotype demonstrated 38% of genotype 1a and 62% of genotype 1b. Eradication rates of 7-day and 14-day regimens with probiotic were 100%, and 88%, respectively. There were no significant difference between eradication rate of 7day and 14-day regimen with or without probiotics. In 7-day regimen, incidence of nausea, abdominal discomfort, diarrhea, and bitter taste were significantly lower in the regimen with probiotic than placebo (7.7%vs.21.8%, 1.9%vs. 14.6%, 0%vs.9.1%, 38.46%vs.69.1%, all p-values<0.05) Conclusions: 7-day moxifloxacin-dexlansoprazole based triple therapy plus probiotic(S. boulardii) as first line therapy provide excellent cure rate (100%) in areas with low clarithromycin resistance, regardless of CYP2C19 and cagA genotypes. Adding probiotic also significantly reduce treatment-related adverse events.
Sa1200 RANDOMIZED PLACEBO-CONTROLLED PHASE III STUDY TO ASSESS THE SAFETY AND EFFICACY OF RIFABUTIN TRIPLE THERAPY (RHB-105) FOR HELICOBACTER PYLORI H. PYLORI INFECTION IN DYSPEPSIA PATIENTS Ira N. Kalfus, Gilead Raday, David Y. Graham RATIONALE: Both Maastricht V and the Kyoto H. pylori consensus recommend eradication therapy for patients with active Hp infections including those with dyspepsia. Standard triple therapy fails to eradicate H. pylori in up to 30% of infected patients. RHB-105 is a new "all-in-one" capsule formulation, comprising a dual antibiotic (rifabutin and amoxicillin) and PPI (omeprazole) drug combination under investigation for the treatment of H. pylori infections. METHODS: This was a Phase III, double-blind, 2:1 randomized, placebo-controlled study of RHB-105 in adult patients complaining of epigastric discomfort that were screened and found to be positive for H. pylori infection via 13C UBT and also by fecal antigen test or gastric biopsy. The primary endpoint was H. pylori eradication confirmed by 13C UBT testing 28-35 days after end of treatment. Secondary and exploratory objectives of the study included safety assessment and CYP2c19 genotyping related to efficacy. RESULTS: Seventy seven subjects received RHB-105 and 41 received FDA mandated placebo for assessment of safety. The Hp eradication rate (based on 13C UBT) in the protocol defined, modified intent-to-treat (mITT) patient population was 89.4% (59/66 subjects). This rate was statistically significantly superior to 70%, P-value < 0.001, which was the reported effectiveness of standard of care (SOC) treatment. Placebo patients and RHB-105 failures underwent physician choice non-rifabutin Hp therapy with eradication rate of 61% (19/31 subjects). Eradication rate with RHB-105 treatment was significantly superior (P = 0.004) to SOC triple therapy 62.9% (17/27). A sensitivity analysis based on the ITT population demonstrated a mean success rate of eradication of Hp of 79%, while a sensitivity analysis based on the PP population showed results similar to the main analysis (success rate = 88.9%, P < 0.001). The AE profile, laboratory values, and other safety assessments did not indicate any safety concerns. Results of CYP 2C19 genotyping in the mITT population showed the majority of RHB-105 treated patients (N = 38, 61.3%) were extensive or rapid metabolizers and 32 (84.2%) successfully eradicated Hp. All of the ultra-rapid (N = 11) and intermediate (N = 13) metabolizers were Hp successes. While not all subjects were assessed, there was no statistically significant difference observed between the success and failure groups based on the CYP 2C19 status (over the different genotypes) for the patients randomized to RHB-105 treatment group (P = 0.123). CONCLUSIONS: RHB-105, a novel" three in one" investigational formulation appeared safe, well-tolerated and more effective than historical SOC treatment regimens as well as physician selected SOC therapy in eradication of H. pylori. A confirmatory Phase III study for this new therapeutic agent is in development.
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Sa1202 EFFICACY AND TOLERABILITY OF TWO QUADRUPLE REGIMENS; BISMUTH, OMEPRAZOLE, METRONIDAZOLE AND AMOXICILLIN OR TETRACYCLINE AS FIRST LINE TREATMENT FOR ERADICATION OF HELICOBACTER PYLORI IN PATIENTS WITH DUODENAL ULCER Hassan Salmanroghani, Roham Salmanroghani, Mahmud Baghbanian, Seyed Masoud Mirvakili Introduction:Evaluation of Helicobacter Pylori (H.Pylori) resistance pattern is not simple, so Classic Bismuth based quadruple therapy Including bismuth, metronidazole, tetracycline and proton pomp inhibitor is recommended regimen as a first line empirical treatment for eradication of H.Pylori in area with high resistance to Metronidazole and Clarithromycin. Intolerance and low compliance are the two major limitations of this regimen. Furthermore, emerging evidences show increasing resistance to tetracycline. The purpose of this study was to evaluate the efficacy and tolerability of replacing tetracycline with high dose of amoxicillin in bismuth based quadruple therapy. Methods: This was a randomized clinical trial study on 228 patients at Sadughi Hospital, an university-affiliated center, Yazd, Iran,during October 2014 to July 2016. H.pylori infection and duodenal ulcer were proved in all patients by rapid urease test and endoscopy, respectively. Patients were prospectively randomized into two groups: One received Metronidazole 500mg, Omprazole 20mg, Bismuth Subcitrate 240mg and Amoxicillin 1000mg,all three times a day(Amoxicillin group;n=113), and second received Metronidazole 500mg and Bismuth subcitrate 240mg, both three times a day and Omeprazole 20mg, twice and Tetracycline HCL 500mg four times a day (Tetracycline group; n=115), both groups get the regimen for 14 days and Patients were fallowed during the treatment to evaluate compliance and side effects. H.Pylori eradication rate was assessed by c13-urease breath test 8 weeks after treatment. We used Chi-square and Fisher's exact tests for statistical analysis. Results: 228 patients were enrolled. 54% were male and the mean age was 40.8(rang 18-78) There was no statistically significant demographic difference between two groups at baseline. Two patients in Amoxicillin group and four patients in Tetracycline group were lost to follow-up and one patient in Amoxicillin group and six patients in Tetracycline group could not tolerate the regimen. Eradication rate by Per protocol analysis was 105 of 110 (95.45%) in amoxicillin group while it was 88 of 105(83.80 %) in Tetracycline group (P value=0.005, OR= 4.01, CI=1.43-11.43). Intention to treat analysis was also 92.9% and 76.51% for Amoxicillin and Tetracycline groups, respectively (P value<0.0001, OR= 4.03, CI=1.74-9.31). Adverse events such as
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POLAPREZINC COMBINED WITH TRIPLE THERAPY FOR HELICOBACTER PYLORI ASSOCIATED GASTRITIS: A PROSPECTIVE, MULTICENTER, RANDOMIZED CLINICAL TRIAL Bei Tan, Hanqing Luo, Hong Xu, Nonghua Lu, Ruihua Shi, Hesheng Luo, Jiansheng Li, Jian-Lin Ren, Yiyou Zou, Yanqing Li, Feng Ji, Jing-Yuan Fang, Jiaming QIan
COMPARISON OF AOC AND AOM TRIPLE, SEQUENTIAL, AND CONCOMITANT THERAPY AS THE FIRST LINE ERADICATION THERAPY FOR HELICOBACTER PYLORI Jin Il Kim Background/Aim: The eradication rates of the AOC standard triple therapy have continuously decreased, because of the widespread development of clarithromycin resistance. We compared the efficacy and adverse events of standard triple, sequential, and concomitant therapy for H. pylori eradication. Method: This was a prospective, multicenter, randomized controlled study involving 1,000 patients diagnosed with H. pylori infection between January 2014 and July 2016 in the five Catholic University Hospitals in affiliation. Diagnosis was made by histological evidence of H. pylori via Warthin-Starry silver staining. We compared 4 treatment regimens and 250 patients were enrolled in each group: the AOC therapy was treated with clarithromycin based triple therapy for 7 days; the AOM therapy was treated with metronidazole based triple therapy for 7 days; the sequential therapy consisted of rabeprazole and amoxicillin for the initial 5 days, followed by rabeprazole, clarithromycin, and metronidazole for the subsequent 5 days; the concomitant therapy consisted of rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. Six weeks following completion of therapy, successful H. pylori eradication was defined by a negative 13C-urea breath test result. Adverse events and drug compliance were evaluated by physicians via direct questioning. Results: A total of 896 patients (224, 223, 218, and 231 patients in the concomitant, sequential, AOM Triple, and AOC standard triple groups, respectively) were analyzed. The mean age of the patients was 55.7 years. There were 464 male and 432 female patients. The eradication rate was significantly higher in the concomitant group (89.7%, 204/224) than in the AOC standard group (78.3%, 181/231), the AOM group (82.6%, 180/218) and the sequential group (85.7%, 191/223) (p=0.006). Drug compliance and adverse events were not statistically different among the three groups. Conclusions: Concomitant therapy appears to be more effective for H. pylori eradication compared to AOC, AOM triple therapy and sequential therapy. There were no statistically different adverse events among the three groups.
Background: Helicobacter pylori is one of the most prevalent global pathogens and treatment failure is increasing due to rising antibiotic resistance. Polaprezinc is a gastric mucosal protective agent complex of zinc and L-carnosine, shown to improve efficacy when combined with triple therapy in Japan. Aim: To compare the clinical efficacy and safety of the polaprezinc combined to triple therapy versus standard triple therapy in the eradication of H. pylori. Methods: This is a randomized, parallel-group controlled, prospective multicenter study in 11 cities of China. Treatment-naïve patients with H. pylori-associated gastritis were randomly assigned to the following groups: Arm A which consists of triple-therapy (omeprazole 20mg, amoxicillin 1g, and clarithromycin 500mg twice daily) plus polaprezinc 75mg twice daily, Arm B which consists of the same triple-therapy plus polaprezinc 150mg twice daily, or Arm C which is the standard triple-therapy for 14 days. Eradication was considered successful if C13 or C14 urea breath test was negative 4 weeks after completion of therapy as the primary outcome. Digestive symptoms improvement 7, 14, 28 days after completion of intervention and rates of adverse effects were the secondary outcomes. Results: 332 enrolled, and 303 patients completed the study, with 106, 96, and 101 patients in Arm A, Arm B, and Arm C. In the intention-to-treat (ITT) analysis, the rate of H. pylori eradication was significantly higher for Arm A (77.0%) and Arm B (75.9%) vs Arm C (58.6%) (p<0.01), whereas there was no difference between Arm A and Arm B (P=0.90) (Table 1, Figure 1). In the per-protocol (PP) analysis, the rate of H. pylori eradication was significantly higher for Arm A (81.1%) and Arm B (83.3%) vs Arm C (61.4%) (P<0.01), while there was no difference between Arm A and Arm B (P=0.62) (Table 1, Figure 1). In all three groups, there were significant symptomatic improvement including abdominal pain, acid reflux, belching, heartburn, bloating, nausea, and vomiting at 7 days, 14 days and 28 days after treatment compared to baseline (P<0.0001). The adverse event rate of Arm B was higher than Arm A (P=0.04) and Arm C (P=0.02), including mild leukopenia, elevated liver enzymes, elevated serum uric acid, and high blood pressure, but there were no serious adverse events. Conclusions: Standard dose polaprezinc combined with standard triple therapy can significantly improve H. pylori eradication rate without an increase in adverse event and is well-tolerated. H. pylori eradication rate in the ITT and PP populations
Sa1197 THE EFFICACY OF PCR-BASED TAILORED ERADICATION THERAPY FOR IN-PATIENTS WITH HELICOBACTER PYLORI INFECTION Young Sin Cho, Su Jung Han, Il-Kwun Chung, Yunho Jung, Tae Hoon Lee, Sang-Heum Park, Sun-Joo Kim Background/Aims: Helicobacter pylori (HP) is the causative pathogen of gastrointestinal diseases such as peptic ulcers and gastric malignancy. The eradication rates of HP infection are decreasing because of increasing resistance to clarithromycin. A previous study showed that a polymerase chain reaction (PCR)-based assay can detect HP and clarithromycin resistance. The aim of this work was to compare the efficacy of PCR-based tailored therapy with that of conventional triple therapy. Methods: From April 2015 to August 2016, 285 consecutive HP-infected patients received PCR-based tailored therapy or standard triple therapy (proton pump inhibitor, clarithromycin, amoxicillin) for 10 days. In the PCR-based tailored therapy group, patients received standard triple therapy or quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) according to clarithromycin resistance confirmed by the PCR-based clarithromycin resistance test, which detects most of the prevalent point mutations (A2143G and A2142G) in HP 23S rRNA. Eradication was assessed using the 13C-urea breath test 6-8 weeks after treatment. Eradication rates and adverse drug effects were compared between groups. Results: The mean age of the patients was 55.5 years. Standard triple therapy was administered to 191 patients and PCR-based tailored therapy to 94 patients. The eradication rates of standard triple therapy and PCR-based tailored therapy were 64.3% (126/191) and 84% (79/94) by intention to treat analysis, respectively (P = 0.005), and 72.4% (126/174) and 88.8% (79/89) by per protocol analysis, respectively (P = 0.002). The complication rates of the PCR-based tailored therapy and standard triple therapy groups were similar (11.1% vs. 12.4%, p=0.629). Conclusions: In HP-infected patients, PCR-based tailored therapy is more effective than conventional triple therapy and can substitute as the first-line HP eradication regimen in regions with high rates of clarithromycin resistance.
ITT, Intention-to-treat; PP, per-protocol; Arm A, polaprezinc 150mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm B, polaprezinc 300mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm C, omeprazole, amoxicillin and clarithromycin for 14 days.
Sa1198 EFFICACY AND SAFETY OF VONOPRAZAN-BASED TRIPLE ERADICATION THERAPY FOR HELICOBACTER PYLORI INFECTION IN 890 PATIENTS Taro Akashi, Daisuke Fukuda, Yutaka Fukuda, Yuko Akazawa, Kazuhiko Nakao Background and aim: Helicobacter pylori infection is the most common infectious disease worldwide, and is a cause of gastric cancer. The first line therapy for H. pylori infection has comprised co-administration of a proton-pump inhibitor (PPI) with two antibiotics, typically, amoxicillin and clarithromycin in Japan. However, with conventional PPIs, 3-5 days are required for lowering intragastric pH to the optimal levels for H.pylori eradication. Vonoprazan, a potassium-competitive acid blocker which rapidly and efficiently inhibits acid secretion, was approved in Japan in 2015. Information regarding Vonoprazan-based H.pylori eradication is still limited. In this study, we investigated the efficacy and tolerability of vonoprazanbased triple eradication therapy for H. pylori infection. Methods: This study included 890 patients (938 cases) who received vonoprazan-based triple eradication therapy for H. pylori infection in a single center. Eight hundred twenty five patients received first line therapy for H. pylori infection with vonoprazan, clarithromycin, and amoxicillin for seven days. One hundred thirteen patients, who had failed first line therapy at our center or other institutions, received second line therapy with vonoprazan, metronidazole and amoxicillin for seven days. Eradication of H. pylori was confirmed by urea breath test in all patients at least a month after the treatment. Eradication rate and side effects were then analyzed. Results: The patients consisted of 510 male (mean age: 58.5±11.3) and 380 female (mean age: 60±11.2). Among the 825 patients who received the first line therapy, H. pylori eradication was achieved in 759 patients (92.0%). Among 113 patients who received the second line
Figure 1 H. pylori eradication rate in the ITT and PP populations ITT, Intention-totreat; PP, per-protocol; Arm A, polaprezinc 150mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm B, polaprezinc 300mg/d combined omeprazole, amoxicillin, clarithromycin for 14 days; Arm C, omeprazole, amoxicillin and clarithromycin for 14 days.* p<0.01
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therapy, H. pylori eradication was achieved in 112 patients (99.1%). The overall rate of grade 2 side effects was 2.9%. The side effects included nausea and diarrhea (1.01%), abdominal pain (0.67%), skin rash (0.67%), heartburn (0.56%), vomiting (0.22%), and constipation (0.22%). There was no distinct difference in rate of side effects between first line therapy and second line therapy. Eradication rate was not significantly different between age groups (<65, 65-74, >74 years) or genders. Conclusions: Our data demonstrate that vonoprazan-based triple therapy is an effective and relatively safe treatment for H. pylori infection.
Sa1201 A MULTICENTER, OPEN-LABEL, RANDOMIZED TRIAL OF VONOPRAZAN VERSUS PPI BASED 7-DAY TRIPLE THERAPY FOR THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION Soichiro Sue, Hirohumi Kuwashima, Isao Arima, Marina Ogushi, Satoshi Nakao, Makoto Naito, Kazuto Komatu, Hiroaki Yamada, Hiroaki Kaneko, Toshihide Tamura, Tomohiko Sasaki, Masaaki Kondo, Wataru Shibata, Shin Maeda Background Vonoprazan is a novel potassium-competitive acid blocker and eradication rate (ER) of vonoprazan (V)-based first line triple therapy with clarithromycin (C) and amoxicillin (A) (VAC) was reported to be 97.6% in patients infected with clarithromycin-susceptible strains in the phaseIII trial. On the other hand, our real-world prospective multi-center cohort study showed under 90% ER for CAM-susceptible (CAM-S) strains (DDW2016, Tu1347). Thus, the aim of this study was to validate the ERs of VAC by multicenter, prospective randomized trial. Method One hundred sixty (160) H. pylori positive by culture test, treatment naïve, patients form 3 hospitals were included. MICs of CAM were determined by agar-dilution methods and the patients were divided into three groups: 41 of CAMresistant (CAM-R) H. pylori, 106 of CAM-S H. pylori and 13 of failure for determination of agar dilution test. CAM-S group were randomized (minimization method with age and sex) to VAC or PAC ; P (lansoprazole 30mg b.i.d., rabeprazole 10mg b.i.d. or esomeprazole 20mg b.i.d.), A (750mg b.i.d.), C (200mg or 400mg b.i.d.). All CAM-R group were eradicated with VAC; V (20mg b.i.d.), A (750mg b.i.d.), C (200mg or 400mg b.i.d.). Average 7.6 weeks after therapy (at least 4weeks) eradication was determined by 13C urea breath test. Safety was evaluated by side effects questionnaire (SEQ) filled by patients during therapy as previously descried. Results Two arms had similar patients demographics (VAC: Female 32%, Age 64±12, PAC: Female 31%, Age 62±13) and no significant differences in clinical background (smoking rate, CAM dose and endoscopic finding). Per-protocol analysis demonstrated no differences between ER of VAC and PAC in CAM-S group (88.9% vs 86.7%, respectively, difference: 2.2%; 95% confidence interval, -10.8%-15.2%). ER of VAC in CAMR group was 82.9%. No significant differences of SEQ score between VAC and PAC were observed: diarrhea, dysgeusia, nausea, anorexia, abdominal pain, heartburn, hives, headache, abdominal fullness, belch, vomiting, and general malaise. Conclusion In the current RCT, we confirmed VAC ER was less than 90% and similar to PAC in patients with CAM-S strains. VAC ER in the patients with CAM-R strains was 82.9% and similar to the phaseIII result (82.0%). These results suggest vonoprazan-based regimen should be applied for the patients in the countries and regions with high frequency of CAM-R strains. Trial registration number UMIN000016337
Sa1199 EFFECTIVENESS OF 7-DAY AND 14-DAY MOXIFLOXACINDEXLANSOPRAZOLE BASED TRIPLE THERAPY AND PROBIOTIC SUPPLEMENT FOR HELICOBACTER PYLORI ERADICATION IN THAI PATIENTS WITH NON-ULCER DYSPEPSIA: A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED STUDY Peranart Chotivitayatarakorn, Sith Siramolpiwat, Soonthorn Chonprasertsuk, Amornnivit Kanokwanvimol, Anupong Tangaroonsanti, Patommatat Bhanthumkomol, Bubpha Pornthisarn, Varocha Mahachai, Ratha-Korn Vilaichone Background: H. pylori is important risk for gastric cancer. Moxifloxacin is used for second line but limited studies as first line therapy. Probiotics might decrease side effects and improve eradication rate but remain uncertain. This study was designed to evaluate efficacy of moxifloxacin-dexlansoprazole based triple therapy with probiotic for first line H. pylori eradication in Thailand. Methods: H. pylori gastritis patients were randomized to receive 7-or14-day regimen with probiotic or placebo. Treatment regimen comprises dexlansoprazole(60mg) twice daily, moxifloxacin(400mg) once daily and clarithromycin MR(1g) once daily. Probiotic was Saccharomyces boulardii in capsule(282.5) prescribed twice daily. CYP2C19 and cagA genotypes along with antibiotic tests were performed. Eradication was defined as negative 13C-UBT 4 weeks after treatment. Results: 112 subjects were enrolled(28 each to 7-and 14-day regimens with probiotic or placebo). Antibiotic tests demonstrated 29% fluoroquinolone, 19% metronidazole and 4% clarithromycin resistances. CYP2C19 genotype revealed 39% rapid metabolizer(RM), 46% intermediate metabolozer(IM) and 10% poor metabolizer(PM). CagA genotype demonstrated 38% of genotype 1a and 62% of genotype 1b. Eradication rates of 7-day and 14-day regimens with probiotic were 100%, and 88%, respectively. There were no significant difference between eradication rate of 7day and 14-day regimen with or without probiotics. In 7-day regimen, incidence of nausea, abdominal discomfort, diarrhea, and bitter taste were significantly lower in the regimen with probiotic than placebo (7.7%vs.21.8%, 1.9%vs. 14.6%, 0%vs.9.1%, 38.46%vs.69.1%, all p-values<0.05) Conclusions: 7-day moxifloxacin-dexlansoprazole based triple therapy plus probiotic(S. boulardii) as first line therapy provide excellent cure rate (100%) in areas with low clarithromycin resistance, regardless of CYP2C19 and cagA genotypes. Adding probiotic also significantly reduce treatment-related adverse events.
Sa1200 RANDOMIZED PLACEBO-CONTROLLED PHASE III STUDY TO ASSESS THE SAFETY AND EFFICACY OF RIFABUTIN TRIPLE THERAPY (RHB-105) FOR HELICOBACTER PYLORI H. PYLORI INFECTION IN DYSPEPSIA PATIENTS Ira N. Kalfus, Gilead Raday, David Y. Graham RATIONALE: Both Maastricht V and the Kyoto H. pylori consensus recommend eradication therapy for patients with active Hp infections including those with dyspepsia. Standard triple therapy fails to eradicate H. pylori in up to 30% of infected patients. RHB-105 is a new "all-in-one" capsule formulation, comprising a dual antibiotic (rifabutin and amoxicillin) and PPI (omeprazole) drug combination under investigation for the treatment of H. pylori infections. METHODS: This was a Phase III, double-blind, 2:1 randomized, placebo-controlled study of RHB-105 in adult patients complaining of epigastric discomfort that were screened and found to be positive for H. pylori infection via 13C UBT and also by fecal antigen test or gastric biopsy. The primary endpoint was H. pylori eradication confirmed by 13C UBT testing 28-35 days after end of treatment. Secondary and exploratory objectives of the study included safety assessment and CYP2c19 genotyping related to efficacy. RESULTS: Seventy seven subjects received RHB-105 and 41 received FDA mandated placebo for assessment of safety. The Hp eradication rate (based on 13C UBT) in the protocol defined, modified intent-to-treat (mITT) patient population was 89.4% (59/66 subjects). This rate was statistically significantly superior to 70%, P-value < 0.001, which was the reported effectiveness of standard of care (SOC) treatment. Placebo patients and RHB-105 failures underwent physician choice non-rifabutin Hp therapy with eradication rate of 61% (19/31 subjects). Eradication rate with RHB-105 treatment was significantly superior (P = 0.004) to SOC triple therapy 62.9% (17/27). A sensitivity analysis based on the ITT population demonstrated a mean success rate of eradication of Hp of 79%, while a sensitivity analysis based on the PP population showed results similar to the main analysis (success rate = 88.9%, P < 0.001). The AE profile, laboratory values, and other safety assessments did not indicate any safety concerns. Results of CYP 2C19 genotyping in the mITT population showed the majority of RHB-105 treated patients (N = 38, 61.3%) were extensive or rapid metabolizers and 32 (84.2%) successfully eradicated Hp. All of the ultra-rapid (N = 11) and intermediate (N = 13) metabolizers were Hp successes. While not all subjects were assessed, there was no statistically significant difference observed between the success and failure groups based on the CYP 2C19 status (over the different genotypes) for the patients randomized to RHB-105 treatment group (P = 0.123). CONCLUSIONS: RHB-105, a novel" three in one" investigational formulation appeared safe, well-tolerated and more effective than historical SOC treatment regimens as well as physician selected SOC therapy in eradication of H. pylori. A confirmatory Phase III study for this new therapeutic agent is in development.
AGA Abstracts
Sa1202 EFFICACY AND TOLERABILITY OF TWO QUADRUPLE REGIMENS; BISMUTH, OMEPRAZOLE, METRONIDAZOLE AND AMOXICILLIN OR TETRACYCLINE AS FIRST LINE TREATMENT FOR ERADICATION OF HELICOBACTER PYLORI IN PATIENTS WITH DUODENAL ULCER Hassan Salmanroghani, Roham Salmanroghani, Mahmud Baghbanian, Seyed Masoud Mirvakili Introduction:Evaluation of Helicobacter Pylori (H.Pylori) resistance pattern is not simple, so Classic Bismuth based quadruple therapy Including bismuth, metronidazole, tetracycline and proton pomp inhibitor is recommended regimen as a first line empirical treatment for eradication of H.Pylori in area with high resistance to Metronidazole and Clarithromycin. Intolerance and low compliance are the two major limitations of this regimen. Furthermore, emerging evidences show increasing resistance to tetracycline. The purpose of this study was to evaluate the efficacy and tolerability of replacing tetracycline with high dose of amoxicillin in bismuth based quadruple therapy. Methods: This was a randomized clinical trial study on 228 patients at Sadughi Hospital, an university-affiliated center, Yazd, Iran,during October 2014 to July 2016. H.pylori infection and duodenal ulcer were proved in all patients by rapid urease test and endoscopy, respectively. Patients were prospectively randomized into two groups: One received Metronidazole 500mg, Omprazole 20mg, Bismuth Subcitrate 240mg and Amoxicillin 1000mg,all three times a day(Amoxicillin group;n=113), and second received Metronidazole 500mg and Bismuth subcitrate 240mg, both three times a day and Omeprazole 20mg, twice and Tetracycline HCL 500mg four times a day (Tetracycline group; n=115), both groups get the regimen for 14 days and Patients were fallowed during the treatment to evaluate compliance and side effects. H.Pylori eradication rate was assessed by c13-urease breath test 8 weeks after treatment. We used Chi-square and Fisher's exact tests for statistical analysis. Results: 228 patients were enrolled. 54% were male and the mean age was 40.8(rang 18-78) There was no statistically significant demographic difference between two groups at baseline. Two patients in Amoxicillin group and four patients in Tetracycline group were lost to follow-up and one patient in Amoxicillin group and six patients in Tetracycline group could not tolerate the regimen. Eradication rate by Per protocol analysis was 105 of 110 (95.45%) in amoxicillin group while it was 88 of 105(83.80 %) in Tetracycline group (P value=0.005, OR= 4.01, CI=1.43-11.43). Intention to treat analysis was also 92.9% and 76.51% for Amoxicillin and Tetracycline groups, respectively (P value<0.0001, OR= 4.03, CI=1.74-9.31). Adverse events such as
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