雷贝拉唑对照、随机、III 期非劣效性研究评价安纳拉唑治疗十二指肠溃疡的疗效和安全性。
Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.
机构信息
Department of Gastroenterology, Changhai Hospital of Navy Military Medical University, Shanghai 200433, China.
Drug Clinical Trial Institution, Changhai Hospital of Navy Military Medical University, Shanghai 200433, China.
出版信息
Chin Med J (Engl). 2022 Dec 20;135(24):2941-2949. doi: 10.1097/CM9.0000000000002508.
BACKGROUND
The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole.
METHODS
In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint.
RESULTS
The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%).
CONCLUSIONS
The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.
REGISTRATION
ClinicalTrials.gov, NCT04215653.
背景
许多质子泵抑制剂（PPIs）在消化性溃疡治疗中的药代动力学和临床行为会因 CYP2C19 遗传多态性而改变。这项非劣效性研究评估了新型 PPI 安纳拉唑与雷贝拉唑相比的疗效和安全性。我们还探讨了幽门螺杆菌（H. pylori）感染状态和 CYP2C19 多态性对安纳拉唑的影响。
方法
在这项多中心、随机、双盲、双模拟、阳性药物平行对照、III 期研究中，中国十二指肠溃疡患者按 1:1 随机接受雷贝拉唑 10mg+安纳拉唑安慰剂或雷贝拉唑安慰剂+安纳拉唑 20mg 每日 1 次，治疗 4 周。主要疗效终点是由盲法独立评估的 4 周溃疡愈合率。次要终点是 4 周时整体和个别十二指肠溃疡症状改善的患者比例。此外，还对 H. pylori 状态和 CYP2C19 多态性的主要终点进行了探索性亚组分析。对安全性进行了不良事件监测。对主要终点进行了非劣效性分析。
结果
该研究共纳入 448 例患者（安纳拉唑组，n=225；雷贝拉唑组，n=223）。安纳拉唑和雷贝拉唑的 4 周愈合率分别为 90.9%和 93.7%（差值，-2.8%[95%置信区间，-7.7%，2.2%]），表明安纳拉唑非劣效于雷贝拉唑。两组患者整体十二指肠溃疡症状均有改善，分别为 90.9%和 92.5%。两组间各症状改善率相似。两组患者的愈合率均不受 H. pylori 状态或 CYP2C19 基因型的影响。安纳拉唑（72/220，32.7%）和雷贝拉唑（84/219，38.4%）治疗组的治疗中出现的不良事件发生率相似。
结论
安纳拉唑在中国十二指肠溃疡患者中的疗效不劣于雷贝拉唑。
登记
ClinicalTrials.gov，NCT04215653。
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