Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)

Gut. 2023 Nov;72(11):2031-2038. doi: 10.1136/gutjnl-2022-329259. Epub 2023 Jul 19.


Background: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain.

Aim: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg).

Methods: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection.

Results: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection.

Conclusions: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Keywords: helicobacter pylori.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Bismuth / adverse effects
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Humans
  • Male
  • Metronidazole / therapeutic use
  • Middle Aged
  • Proton Pump Inhibitors
  • Registries


  • Bismuth
  • Anti-Bacterial Agents
  • Metronidazole
  • Proton Pump Inhibitors
  • Amoxicillin