Vonoprazan Prevents Ulcer Recurrence During Long-Term NSAID Therapy: Randomised, Lansoprazole-Controlled Non-Inferiority and Single-Blind Extension Study

Gut. 2018 Jun;67(6):1042-1051. doi: 10.1136/gutjnl-2017-314010. Epub 2017 Oct 7.

Abstract

Objective: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.

Design: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.

Results: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified.

Conclusion: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg).

Trial registration numbers: NCT01452750, NCT01456260; Results.

Keywords: NSAIDs; lansoprazole osteoarthritis; non-inferiority; peptic ulcer; potassium-competitive acid blockers; rheumatoid arthritis; vonoprazan.

Publication types

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

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Ulcer Agents / therapeutic use*
  • Double-Blind Method
  • Equivalence Trials as Topic
  • Female
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / etiology
  • Humans
  • Lansoprazole / adverse effects
  • Lansoprazole / therapeutic use*
  • Male
  • Middle Aged
  • Peptic Ulcer / drug therapy*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Recurrence
  • Secondary Prevention
  • Single-Blind Method
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Survival Analysis
  • Treatment Outcome

Substances

  • 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

Associated data

  • ClinicalTrials.gov/NCT01452750
  • ClinicalTrials.gov/NCT01456260