Abstract：
OBJECTIVE: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis.
METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety.
RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups.
CONCLUSIONS: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety.
RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups.
CONCLUSIONS: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
摘要：
目的：高剂量质子泵抑制剂（PPI）治疗已被推荐用于预防高危消化性溃疡（PU）止血后再出血。Vonoprazan已被证明在各种酸相关疾病中不劣于PPI。本研究旨在比较vonoprazan与PPI预防高危PU止血后再出血的疗效。
方法：多中心，随机化，在6个中心进行了非劣效性研究.根据标准方案进行内镜前和内镜治疗。止血成功后,高危PU出血患者(ForrestIa/Ib级，IIa/IIb）随机分为1：1接受vonoprazan（20mgBID，持续3天，然后20-mgOD，持续28天）或高剂量PPI（泮托拉唑静脉输注8mg/小时，持续3天，然后奥美拉唑20mgBID28天）。主要结果是30天再出血率。次要结果包括3天和7天再出血率，全因和出血相关死亡率，抢救治疗率，输血,住院时间,和安全。
结果：在194名患者中，基线特征，出血的严重程度，两组溃疡分期相当。vonoprazan和PPI组的30天再出血率分别为7.1％（7/98）和10.4％（10/96），分别确认了vonoprazan对PPI的非劣效性（在10％范围内）（％风险差异=-3.3；95％置信区间=-11.2，4.7；P<0.001）。vonoprazan组的3天和7天再出血率仍然不劣于PPI（通过Farrington和Manning检验P<0.001）。两组之间的所有次要结局也具有可比性。
结论：高危PU出血患者，vonoprazan预防30日再出血的疗效不劣于静脉PPI.
方法：多中心，随机化，在6个中心进行了非劣效性研究.根据标准方案进行内镜前和内镜治疗。止血成功后,高危PU出血患者(ForrestIa/Ib级，IIa/IIb）随机分为1：1接受vonoprazan（20mgBID，持续3天，然后20-mgOD，持续28天）或高剂量PPI（泮托拉唑静脉输注8mg/小时，持续3天，然后奥美拉唑20mgBID28天）。主要结果是30天再出血率。次要结果包括3天和7天再出血率，全因和出血相关死亡率，抢救治疗率，输血,住院时间,和安全。
结果：在194名患者中，基线特征，出血的严重程度，两组溃疡分期相当。vonoprazan和PPI组的30天再出血率分别为7.1％（7/98）和10.4％（10/96），分别确认了vonoprazan对PPI的非劣效性（在10％范围内）（％风险差异=-3.3；95％置信区间=-11.2，4.7；P<0.001）。vonoprazan组的3天和7天再出血率仍然不劣于PPI（通过Farrington和Manning检验P<0.001）。两组之间的所有次要结局也具有可比性。
结论：高危PU出血患者，vonoprazan预防30日再出血的疗效不劣于静脉PPI.
