The primary aim of this study is to evaluate the efficacy and safety of novel P-CAB (tegoprazan 50 mg once daily) as compared with standard PPI (rabeprazole 20 mg once daily) for protection of GI events in patients with known cardiac and vascular disease receiving chronic use of antithrombotic drugs (either antiplatelets, OAC, and its combinations) who are at high GI bleeding risk. The primary hypothesis is that P-CAB (experimental arm) would non-inferior to PPI (standard arm) with respect to the rate of the primary composite end point of GI events at 12 months after randomization.
Patients 19 years of age or older with known cardiac and vascular disease who are receiving chronic use of antithrombotic drugs (either antiplatelets, oral anticoagulant (OAC), and its combinations). Specific clinical conditions that may confer a need for long-term antithrombotic therapy may include documented coronary artery disease (stable or unstable angina, acute coronary syndrome, a history of myocardial infarction, or any coronary revascularization), documented cerebrovascular disease (stroke or transient ischemic attack), known peripheral arterial disease or a history of peripheral arterial revascularization, atrial fibrillation, or valvular heart disease requiring interventions (transcatheter aortic valve replacement or transcatheter mitral-valve repair). Concomitant use of a proton pump inhibitor is strongly recommended in patients receiving aspirin monotherapy, DAPT (dual antiplatelet therapy; aspirin plus any P2Y12 inhibitors), DAT (dual antithrombotic therapy; antiplatelet drug plus OAC), TAT (triple antithrombotic therapy; DAPT plus OAC), or OAC monotherapy (warfarin or direct oral anticoagulants) who are at high risk of GI bleeding in order to reduce the risk of gastric bleed or GI events. Based on clinical guidelines, the use of P2Y12 inhibitor monotherapy (i.e. clopidogrel, ticagrelor, or prasugrel) is not considered in trial enrollment.
Age ≥65 years
Concomitant use of OAC and any antiplatelet therapy (mono or DAPT) (i.e., DAT or TAT)
Long-term use of oral NSAIDs (non-steroidal anti-inflammatory drugs) or steroids or high-dose NSAID therapy even during a relatively short-term period.
Active bleeding at the time of inclusion or a history of hereditary or acquired hemostatic disorder
Any clinical contraindication to using of antithrombotic therapies (antiplatelet agents or OAC)
Concurrent use of PPI or P-CAB within 4 weeks before randomization
Hemodynamically unstable conditions at the time of inclusion: cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, or congestive heart failure (New York Heart Association class IV).
Parallel
PPI
Drugrabeprazole 20mg + tegoprazan 50 mg placebo, once daily.
P-CAB 50
Drugtegoprazan 50 mg + rabeprazole 20mg placebo, once daily.
The time from randomization to the first occurrence of a composite endpoint of upper GI clinical events, including during the treatment period
This composite outcome included: 1. Overt upper gastrointestinal bleeding (confirmed by means of upper endoscopy or computed tomography); 2. Overt upper gastrointestinal bleeding of unknown origin; 3. Bleeding of presumed occult gastrointestinal origin with a documented decrease in haemoglobin of ≥ 2 g/dL or decrease in hematocrit ≥ 10% from baseline; 4. Symptomatic gastroduodenal ulcer (confirmed by means of endoscopy or computed tomography) without evidence of gastrointestinal bleeding; 5. Persistent pain of presumed gastrointestinal origin (duration ≥ 3 days) with underlying multiple erosive disease (5 or more gastroduodenal erosions confirmed by means of endoscopy); 6. Gastrointestinal obstruction; or 7. Gastrointestinal perforation. A composite endpoint is an endpoint that is a combination of multiple clinical endpoints. An event is considered to have occurred if any of several different events is observed.
The event rate of overt upper gastrointestinal bleeding (confirmed by means of upper endoscopy or computed tomography)
The event rate of overt upper GI bleeding of unknown origin
The event rate of bleeding of presumed occult GI origin with the documented decrease in Hgb of≥2g/dL or decrease in hematocrit≥10% from baseline
The event rate of symptomatic gastroduodenal ulcer(confirmed by means of endoscopy or computed tomography) without evidence of GI bleeding
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Duk-Woo Park, MD
Lead sponsor
Asan Medical Center
Sponsor institution
