title: Comparison of sequential therapy and amoxicillin/tetracycline containing bismuth quadruple therapy for the first-line eradication of Helicobacter pylori: a prospective, multi-center, randomized clinical trial.
abstract: BACKGROUND
  The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy.
  
  
  METHODS
  In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication.
  
  
  RESULTS
  Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040).
  
  
  CONCLUSIONS
  Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.|Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Ju Yup
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. nayoungkim49@empas.com.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Gyeongsangnam-do, South Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, South Korea.
authors.forename: Gwang Ho
authors.initials: GH
authors.lastname: Baik
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.
authors.forename: Ki-Nam
authors.initials: KN
authors.lastname: Shim
authors.affiliation: Departments of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, South Korea.
authors.forename: Suck Chei
authors.initials: SC
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Gwang Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Bong Eun
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul, South Korea.
authors.forename: Yunju
authors.initials: Y
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine and Research Institute, Soonchunhyang University College of Medicine, Bucheon, South Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Hong
mesh_terms: D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000863:Antacids / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001729:Bismuth / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D005756:Gastritis / Q000188:drug therapy* / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011446:Prospective Studies; D013752:Tetracycline / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000863:Antacids; D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D013752:Tetracycline; D001729:Bismuth
keywords: Amoxicillin; Bismuth; Eradication; Helicobacter pylori; Quadruple; Tetracycline