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

Abstract

ObjectiveCompare 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.DesignDouble-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.ResultsThe 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.ConclusionVonoprazan (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 numbersNCT01452763; NCT01456247.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study)

“…No human subjects treated with vonoprazan in pre‐approval clinical studies developed NETs . In recent studies, vonoprazan administered at 10 or 20 mg OD for up to 1 year or even longer increased serum gastrin level but was tolerated well in patients with healed GERD or peptic ulcer . Nonetheless, as 2‐ to 3‐times higher serum gastrin levels were sustained in subjects treated with vonoprazan compared with those treated with lansoprazole, attention should still be paid to possible occurrence of severe hypergastrinemia that may induce NETs during vonoprazan treatment, particularly long‐term treatment.…”

“…15 In recent studies, vonoprazan administered at 10 or 20 mg OD for up to 1 year or even longer increased serum gastrin level but was tolerated well in patients with healed GERD or peptic ulcer. [44][45][46] Nonetheless, as 2-to 3-times higher serum gastrin levels were sustained in subjects treated with vonoprazan 47,48 and may be used to monitor the risk of these malignancies during long-term acid suppression by vonoprazan.…”

Current states of prevention of drug-induced gastroduodenal ulcer in real clinical practice: a cross-sectional study

“…Recently, the efficacy of vonoprazan for prevention of NSAID and LDA-induced gastroduodenal ulcer has been reported in Japan. (21,22) In cases under treatment with concomitant anti-ulcer drugs, we found that a significant higher rate of use of single NSAIDs in non-bleeding cases than in bleeding cases, and we also found a significant higher rate of use of LDA or other antiplatelet drugs in bleeding cases. These results may indicate that, in contrast to patients taking LDA or other antiplatelet drugs, those taking a single NSAID have a lower risk of gastroduodenal bleeding while under preventive treatment.…”

Vonoprazan, aspirin and NSAIDs: new era in acid inhibition and gastroprotection

“…The proportions of patients with recurrent peptic ulcers within 24 weeks were 3.3%, 3.4% and 5.5% for vonoprazan 10 mg, 20 mg, and lansoprazole 15 mg, respectively. Similarly, and in patients using aspirin, Dr Kawai and colleagues reported that 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 9. Both sets of authors concluded that the non-inferiority of vonoprazan to lansoprazole 15 mg was verified.…”