Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study

Gut. 2018 Jun;67(6):1033-1041. doi: 10.1136/gutjnl-2017-314852. Epub 2017 Dec 1.


Objective: Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study.

Design: Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations.

Results: The 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study.

Conclusion: Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated.

Trial registration numbers: NCT01452763; NCT01456247.

Keywords: aspirin; cardiovascular diseases; peptic ulcer; potassium-competitive acid blockers; proton pump inhibitors.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Ulcer Agents / adverse effects
  • Anti-Ulcer Agents / therapeutic use*
  • Aspirin / adverse effects
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / etiology
  • Humans
  • Japan
  • Lansoprazole / adverse effects
  • Lansoprazole / therapeutic use*
  • Male
  • Middle Aged
  • Peptic Ulcer / drug therapy*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Recurrence
  • Secondary Prevention
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome


  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Pyrroles
  • Sulfonamides
  • Lansoprazole
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT01452763
  • ClinicalTrials.gov/NCT01456247