Comparison of Vonoprazan versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding after Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial

Abstract

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 aims to compare the efficacy of vonoprazan versus PPI for preventing high-risk PU rebleeding after hemostasis. 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 BID for 3 days, then 20-mg OD for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/hour for 3 days, then omeprazole 20-mg BID 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. Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable among the two groups. The 30-day rebleeding rate in vonoprazan and PPI groups were 7.1% (7/98) and 10.4% (10/96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference= -3.3; 95% confidence interval = -11.2, 4.7; P<0.001). The 3-day and 7-day rebleeding rates in vonoprazan group remained noninferior to PPI (P< 0.001 by Farrington and Manning test). All secondary outcomes were also comparable between the two groups. In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI.