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

Abstract

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.

Figure 1

Patient disposition in the double-blind and extension studies. (A) 24-Week study. (B) Extension study. The patients completed the double-blind study were enrolled consecutively until the enrolments reached the targeted number of patient. By then, the enrolment was ended. LDA, low-dose aspirin.

Figure 2

Kaplan-Meier estimates of the cumulative incidence of (A) peptic ulcer recurrence and (B) bleeding in the stomach or duodenum in patients treated with lansoprazole 15 mg (dotted line), vonoprazan 10 mg (solid line) or vonoprazan 20 mg (thick solid line). The numbers of patients at risk for each treatment group are shown in table 1.

Figure 3

Mean (SD) serum gastrin levels, pepsinogen levels and pepsinogen I/II ratio in patients treated for up to 52 weeks with lansoprazole 15 mg (○), vonoprazan 10 mg (▲), or vonoprazan 20 mg (●). (A) Serum gastrin, (B) pepsinogen I, (C) pepsinogen II and (D) pepsinogen I/II ratio.