Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg)

Clin Gastroenterol Hepatol. 2022 Oct;20(10):2243-2257. doi: 10.1016/j.cgh.2021.12.025. Epub 2021 Dec 23.


Background & aims: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe.

Methods: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality.

Results: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization.

Conclusions: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Keywords: Bismuth; Clarithromycin; Helicobacter pylori; Levofloxacin; Rescue.

Publication types

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

MeSH terms

  • Adult
  • Amoxicillin
  • Anti-Bacterial Agents / therapeutic use
  • Bismuth
  • Clarithromycin / therapeutic use
  • Drug Therapy, Combination
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Humans
  • Levofloxacin
  • Moxifloxacin / therapeutic use
  • Penicillins / adverse effects
  • Prospective Studies
  • Proton Pump Inhibitors
  • Quinolones* / therapeutic use
  • Registries
  • Tetracycline / therapeutic use


  • Anti-Bacterial Agents
  • Penicillins
  • Proton Pump Inhibitors
  • Quinolones
  • Levofloxacin
  • Amoxicillin
  • Tetracycline
  • Clarithromycin
  • Bismuth
  • Moxifloxacin

Associated data

  • ClinicalTrials.gov/NCT02328131