Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

Gut. 2016 Sep;65(9):1439-46. doi: 10.1136/gutjnl-2015-311304. Epub 2016 Mar 2.

Abstract

Objective: The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.

Design: A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment.

Results: Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated.

Conclusion: Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer.

Trial registration number: NCT01505127.

Keywords: ANTIBIOTIC THERAPY; CLINICAL TRIALS; HELICOBACTER PYLORI - TREATMENT; HELICOBACTER PYLORI INFECTION.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amoxicillin / administration & dosage
  • Amoxicillin / adverse effects
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Breath Tests / methods
  • Clarithromycin / administration & dosage
  • Clarithromycin / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Monitoring / methods
  • Drug Therapy, Combination / methods
  • Female
  • Helicobacter Infections* / complications
  • Helicobacter Infections* / diagnosis
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori* / drug effects
  • Helicobacter pylori* / isolation & purification
  • Humans
  • Lansoprazole* / administration & dosage
  • Lansoprazole* / adverse effects
  • Male
  • Metronidazole / administration & dosage
  • Metronidazole / adverse effects
  • Middle Aged
  • Peptic Ulcer / diagnosis
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / etiology
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects
  • Pyrroles* / administration & dosage
  • Pyrroles* / adverse effects
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Treatment Outcome

Substances

  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Pyrroles
  • Sulfonamides
  • Lansoprazole
  • Metronidazole
  • Amoxicillin
  • Clarithromycin

Associated data

  • ClinicalTrials.gov/NCT01505127