摘要
目的：本研究旨在观察埃索美拉唑在治疗非静脉曲张性上消化道出血的疗效,目的是通过临床试验获得国家食品药品监督管理局对埃索美拉唑治疗非静脉曲张性上消化道出血适应症的批准。
方法：本研究是一项多中心、随机、双盲、双模拟、平行组活性药物对照的非劣效性设计临床研究,以评估埃索美拉唑钠40 mg q12h或奥美拉唑钠40mg q12h静脉滴注5天对治疗急性非静脉曲张性上消化道出血受试者的疗效及安全性。研究在全国13家经国家食品药品监督管理局批准的消化科临床试验基地进行,共有448例经内镜证实的急性非静脉曲张性上消化道出血的患者参与本项临床试验研究。
结果：主要疗效终点,在ITT(意向治疗)人群中,两组治疗5天内临床上无消化道出血征象的受试者百分比均超过了95%,埃索美拉唑组和奥美拉唑组分别为95.3%和97.2%。在急性非静脉曲张性上消化道出血受试者中,埃索美拉唑组疗效不劣于奥美拉唑组(p=0.3699)。PP(符合方案)人群的结果与ITT人群结果相似,埃索美拉唑组和奥美拉唑组的有效止血率分别为97.1%和98%(p=0.6297)。
两治疗组的次要疗效指标之间差异没有统计学意义。埃索美拉唑组和奥美拉唑组治疗72小时无上消化道出血征象的受试者百分比分别为87.2%和90.8%(p=0.3146)。两组受试者上消化道出血征象停止的中位时间均为48小时(p=0.4161)。奥美拉唑组中有1例在研究期间因上消化道出血需要外科手术,而埃索美拉唑组则没有(p=0.244)。埃索美拉唑组和奥美拉唑组在5天(p=0.1591)和72小时(p=0.2127)的治疗期内的中位输血量分别均为400ml和300ml。
结论：在ITT与PP人群中,就急性非静脉曲张性上消化道出血的受试者而言,埃索美拉唑组治疗五天临床上无消化道出血征象的受试者百分比不劣于奥美拉唑组,且均超过了95%。总体而言,两种药物均有很好的耐受性。两治疗组所报告的不良事件发生频率及发生强度均较低。研究中没有死亡病例。两组药物的安全性数据未显示有差异。不良事件两治疗组中分布均衡。
OBJECTIVE:The objective of this study is to evaluate the efficacy of Esomeprazole infusion in subjects with acute non-variceal upper gastrointestinal bleeding. The study is performed in order to meet the regulatory requirements for the indication of treatment of non-variceal upper GI bleeding using Esomeprazole.
METHOD:The study is carried out as a multi-center, randomized, double-blind, double dummy, parallel-group, active-controlled non-inferiority study to assess the efficacy and safety of Esomeprazole 40 mg q12h infusion or Omeprazole 40 mg q12h infusion for 5 days in subjects with acute non-variceal upper gastrointestinal bleeding. It is conducted in 13 SFDA certified gastrointestinal department. Totally 448 patients with acute non-variceal upper gastrointestinal bleeding, verified by endoscopies at baseline was randomised.
RESULT:The primary endpoint, the proportion of no clinically significant upper gastrointestinal bleeding after 5 days treatment, exceeded 95% in both treatment groups in ITT population, with 95.3% and 97.2% in Esomeprazole group and Omeprazole group respectively. Esomeprazole group is non- inferior to Omeprazole group in subjects with acute non-variceal upper gastrointestinal bleeding. (p=0.3699) Compared with ITT population, the result in PP population was similar with 97.1% vs 98% in Esomeprazole and Omeprazole treatment groups respectively (p=0.6297).
In terms of second efficacy results, no statistical significant differences were shown between two treatment groups. After 72 hours treatment, the proportion of no clinically significant upper gastrointestinal bleeding in Esomeprazole and Omeprazole group were 87.2% and 90.8 respectively (p=0.3146). The median time to absence of clinically significant upper gastrointestinal bleeding was same with 48 hours in both treatment groups (p=0.4161). One subject in Omeprazole group was needed surgery during the treatment period, while none in Esomeprazole group had this need (p=0.244). The median numbers of transfused blood units in Esomeprazole and Omeprazole group were 400 ml and 300 ml, respectively within both 5 days (p=0.1591) and 3 days (p=0.2127).
CONCLUSION:In both ITT and PP population, the proportion of no clinically significant upper gastrointestinal bleeding after 5-day treatment in Esomeprazole group was non-inferior to Omeprazole group in subjects with acute non-variceal upper gastrointestinal bleeding, and exceeded 95% in both treatment groups. Adverse events were evenly distributed across the treatment groups and both drugs were well tolerated.
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