title: Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.
abstract: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori.
  
  
  
  In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879.
  
  
  
  Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy.
  
  
  
  Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered.
  
  
  
  National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Jyh-Ming
authors: JM
authors: Liou
authors: Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
authors: Yu-Jen
authors: YJ
authors: Fang
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chieh-Chang
authors: CC
authors: Chen
authors: Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan.
authors: Ming-Jong
authors: MJ
authors: Bair
authors: Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan.
authors: Chi-Yang
authors: CY
authors: Chang
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yi-Chia
authors: YC
authors: Lee
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Mei-Jyh
authors: MJ
authors: Chen
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chien-Chuan
authors: CC
authors: Chen
authors: Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan.
authors: Cheng-Hao
authors: CH
authors: Tseng
authors: Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan.
authors: Yao-Chun
authors: YC
authors: Hsu
authors: Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
authors: Ji-Yuh
authors: JY
authors: Lee
authors: Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan.
authors: Tsung-Hua
authors: TH
authors: Yang
authors: Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Jiing-Chyuan
authors: JC
authors: Luo
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Chun-Chao
authors: CC
authors: Chang
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
authors: Chi-Yi
authors: CY
authors: Chen
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
authors: Po-Yueh
authors: PY
authors: Chen
authors: Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chia-Tung
authors: CT
authors: Shun
authors: Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors: Wen-Feng
authors: WF
authors: Hsu
authors: Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors: Wen-Hao
authors: WH
authors: Hu
authors: Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors: Yen-Nien
authors: YN
authors: Chen
authors: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; National Cheng Kung University Medical Center, Tainan, Taiwan.
authors: Bor-Shyang
authors: BS
authors: Sheu
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Jaw-Town
authors: JT
authors: Lin
authors: Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Jeng-Yih
authors: JY
authors: Wu
authors: Department of Medicine, St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia.
authors: Emad M
authors: EM
authors: El-Omar
authors: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: mingshiang@ntu.edu.tw.
authors: Ming-Shiang
authors: MS
authors: Wu
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000863:Antacids / Q000008:administration & dosage* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001944:Breath Tests; D017291:Clarithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000706:statistics & numerical data*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013624:Taiwan; D013752:Tetracycline / Q000008:administration & dosage / Q000627:therapeutic use; D014508:Urea / Q000378:metabolism
chemical_list: D000863:Antacids; D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D014508:Urea; D013752:Tetracycline; D017291:Clarithromycin; C002791:bismuth tripotassium dicitrate