title: High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection.
abstract: OBJECTIVE
  The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori.
  
  
  METHODS
  We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes.
  
  
  RESULTS
  In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence.
  
  
  CONCLUSIONS
  HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: jcyang47@ntu.edu.tw.
authors.forename: Jyh-Chin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Statistics, National Taipei University, New Taipei City, Taiwan.
authors.forename: Hong-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
authors.forename: Jin-De
authors.initials: JD
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: jykao@med.umich.edu.
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.affiliation: Department of Forensic Medicine and Pathology, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lu
authors.affiliation: Department of Integrated Diagnostics and Therapeutics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Bor-Ru
authors.initials: BR
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
authors.affiliation: Department of Internal Medicine, Non-Profit Proprietary Miners Hospital, Keelung, Taiwan.
authors.forename: Lin-Chih
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, New Taipei City Hospital San Chung Branch, New Taipei City, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Yeh
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Kuo
authors.affiliation: Department of Integrated Diagnostics and Therapeutics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Tung
authors.affiliation: Department of Internal Medicine, West Garden Hospital, Taipei, Taiwan.
authors.forename: Yew-Loong
authors.initials: YL
authors.lastname: Leong
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Teh-Hong
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jau-Min
authors.initials: JM
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors
keywords: Bacterial Infection; Microbe; PPI; Proton Pump Inhibitor; Stomach