Potassium-competitive acid blocker vs proton-pump inhibitor in patients receiving antithrombotic therapy who are at high risk for gastrointestinal bleeding: Rationale and design of the randomized PROTECT-HBR trial

Abstract

Background Concomitant use of proton pump inhibitor (PPI) is recommended in patients receiving chronic antithrombotic therapy who are at high risk of gastrointestinal (GI) bleeding. However, long-term safety and efficacy of chronic PPI use have been concerned. Potassium-competitive acid blocker (P-CAB) is a novel class of acid suppressants, providing more acid stability, rapid onset of action, less variability with CYP2C19 polymorphisms, and longer duration of action than PPI. Design The PROTECT-HBR trial is a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial. Approximately 3320 patients with known cardiac or vascular disease receiving antithrombotic drugs (either antiplatelet or anticoagulant agents) and who are at high risk of GI bleeding will be randomized to P-CAB (tegoprazan 50mg once daily) or PPI (rabeprazole 20mg once daily) for up to 12 months. The primary endpoint is a composite outcome of upper GI clinical events, including overt or occult GI bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation, at 12 months. Secondary endpoints also included cardiovascular events and safety outcomes. Results As of December 2024, approximately 1460 patients were enrolled from 32 participating sites in South Korea. The complete enrollment is anticipated at the mid-or late-term of 2025, and the primary results will be available by 2027. Conclusion PROTECT-HBR is a large-scale, multicenter, clinical trial, which will provide a pivotal comparison of the efficacy and safety of novel P-CAB, tegoprazan with those of PPI, rabeprazole in patients with documented cardiac or vascular disease receiving chronic antithrombotic drugs and at high risk of GI bleeding. Clinical Trial Registration Potassium-Competitive Acid Blocker versus pROton-Pump Inhibitor for Gastropro-TECTion Strategies In Patients at High GastroIntestinal Bleeding Risk Receiving Antithrombotic Therapy (PROTECT-HBR): NCT04416581. (Am Heart J 2025