Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial

Am J Gastroenterol. 2016 Mar;111(3):381-7. doi: 10.1038/ajg.2015.439. Epub 2016 Feb 2.


Objectives: The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment.

Methods: This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test.

Results: The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism.

Conclusions: Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori (

Trial registration number: NCT01537055).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amoxicillin* / administration & dosage
  • Amoxicillin* / adverse effects
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Drug Administration Schedule
  • Drug Monitoring / methods
  • Drug Therapy, Combination / methods
  • Female
  • Helicobacter Infections* / diagnosis
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori* / drug effects
  • Helicobacter pylori* / isolation & purification
  • Humans
  • Lansoprazole* / administration & dosage
  • Lansoprazole* / adverse effects
  • Levofloxacin* / administration & dosage
  • Levofloxacin* / adverse effects
  • Male
  • Metronidazole* / administration & dosage
  • Metronidazole* / adverse effects
  • Middle Aged
  • Stomach Diseases* / drug therapy
  • Stomach Diseases* / microbiology
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Lansoprazole
  • Metronidazole
  • Levofloxacin
  • Amoxicillin

Associated data

  • ClinicalTrials.gov/NCT01537055