Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan.
Takeda Development Center, Takeda Pharmaceutical Company Ltd, Osaka, Japan.
Gut. 2018 Jun;67(6):1033-1041. doi: 10.1136/gutjnl-2017-314852. Epub 2017 Dec 1.
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.
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.
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.
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.
NCT01452763; NCT01456247.
在一项为期 24 周的研究中比较沃诺拉赞和兰索拉唑在预防低剂量阿司匹林（LDA）相关消化性溃疡复发方面的疗效和安全性，并在单独的研究中进行长期扩展治疗。
双盲、随机、非劣效性研究；在 104 个日本地点进行的单盲扩展研究，包括 621 例（扩展研究中 439 例）有消化性溃疡病史且需要长期 LDA 治疗的患者。患者按 1:1:1（计算机生成）随机分配，接受兰索拉唑 15mg（n=217）、沃诺拉赞 10mg（n=202）或沃诺拉赞 20mg（n=202），每日 1 次，治疗 24 周（双盲）和最长 2 年（扩展）。主要测量指标为：24 周（主要结局；双盲）和 12 周消化性溃疡复发率、24 周胃肠道出血率、消化性溃疡复发和胃肠道出血的累积发生率、治疗期间发生的不良事件、实验室结果、血清胃泌素和胃蛋白酶原 I/II 浓度。
兰索拉唑 15mg、沃诺拉赞 10mg 和沃诺拉赞 20mg 组 24 周消化性溃疡复发率分别为 2.8%、0.5%和 1.5%。沃诺拉赞与兰索拉唑相当（法林顿和曼宁检验：差值 8.7%，显著性水平 2.5%）。在扩展研究的事后分析中，与兰索拉唑 15mg 相比，沃诺拉赞 10mg 显著降低了消化性溃疡复发率（对数秩检验，P=0.039），但沃诺拉赞 20mg 差异无统计学意义（P=0.260）。在 24 周研究和扩展研究中，与兰索拉唑相比，两种剂量的沃诺拉赞胃肠道出血率均较高。
沃诺拉赞（10mg 和 20mg）在预防 LDA 治疗期间消化性溃疡复发方面与兰索拉唑（15mg）同样有效，长期安全性相似，且耐受良好。
NCT01452763；NCT01456247。
