Potassium-Competitive Acid Blocker Versus pROton-Pump Inhibitor for GastroproTECTion Strategies In Patients at High Gastro-Intestinal Bleeding Risk Receiving Antithrombotic Therapy

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The primary aim of this study is to evaluate the efficacy and safety of P-CAB (tegoprazan 50 mg once daily) as compared with PPI (rabeprazole 20 mg once daily) for protection of GI events in patients with cardiovascular disease receiving antiplatelet and oral anticoagulant therapy who are at high GI bleeding risk. The primary hypothesis is that P-CAB (experimental arm) is non-inferior to PPI (standard arm) with respect to the rate of the primary composite endpoint of GI events at 6 months.

In addition, as exploratory nature, we evaluate the efficacy and safety of low-dose P-CAB (tegoprazan 25 mg once daily) as compared with standard-dose P-CAB (tegoprazan 50 mg once daily) and standard-dose PPI (rabeprazole 20 mg).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duk-Woo Park, MD

Criteria

Inclusion Criteria:

1. 1. Patients 19 years of age or older with known cardiovascular disease in whom a requirement for chronic use of antithrombotic therapy (either antiplatelets or OAC). Specific clinical conditions that may confer a need for long-term antithrombotic therapy may include acute coronary syndrome and those with a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, peripheral arterial disease, or atrial fibrillation. Concomitant use of a proton pump inhibitor is recommended in patients receiving aspirin monotherapy, DAPT (dual antiplatelet therapy), DAT (dual antithrombotic therapy), TAT (triple antithrombotic therapy.), or OAC monotherapy who are at high risk of gastrointestinal bleeding in order to reduce the risk of gastric bleeds.

2. On the basis of clinical guidelines and expert consensus documents, we defined study population with increased risk of gastrointestinal bleeding if they had a least 1 or more criteria of the following characteristics. Eligible patients for randomization must meet at least 1 characteristic of these criteria:

*Definition of patients who are at high risk of gastrointestinal bleeding

1. Age ≥65 years

2. Concomitant use of OAC and any antiplatelet therapy (mono or DAPT) (i.e., DAT or TAT)

3. 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.

4. History of prior GI bleeding events at any time

5. History of a previously complicated ulcer

6. History of peptic ulcer disease or a previously uncomplicated ulcer

7. Documented Helicobacter pylori infection

3. Patients who voluntarily participated in the written agreement

Exclusion Criteria:

1. Active bleeding at the time of inclusion or a history of hereditary or acquired hemostatic disorder

2. Any clinical contraindication to use of antithrombotic therapies (antiplatelet agents or OAC)

3. 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).

4. Baseline severe anaemia (Hgb <8 g/dl at baseline) or transfusion within 4 weeks before randomization

5. Baseline severe thrombocytopenia (platelet count <50,000/mm3)

6. Renal failure-dependent on dialysis or severe renal insufficiency (creatinine clearance <15 ml/min)

7. Severe chronic liver disease (defined as variceal haemorrhage, ascites, hepatic encephalopathy, or jaundice)

8. Hypersensitivity or contraindication to PPI, P-CAB, any of the product components, or substituted benzimidazoles

9. Systemic treatment with strong CYP 3A4 and p-glycoprotein (P-GP) inhibitors (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir)

10. Patients who take atazanavir, nelfinavir or rilpivirine-containing products (see Drug-Drug interaction section)

11. Clinically significant laboratory abnormality at screening (estimated glomerular filtration rate (eGFR) <15 mL/min or elevated liver enzyme [AST, ALT, ALP, total bilirubin] > 3 times upper normal limit [UNL] or any other condition that, in the opinion of the Investigator, precludes participation in the study

12. Any known or suspected malignancy

13. Subjects with non-cardiac co-morbidities with life expectancy less than 12 months

14. Women who are pregnant or breastfeeding or female subjects, premenopausal who are not surgically sterile, or, if sexually active not practising an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, who have a positive pregnancy test at screening

15. Participation in another clinical study within 12 months. However, where at least one or more condition are satisfied, it could be an exception according to an investigator's discretion;

1. Participated in the observational study expected no effect on the safety and/or effectiveness evaluation of this trial

2. Screening failed before any interventional factor is involved

3. Participated in academic trials like strategic or medical device comparison studies conducting under standard therapy provided that there is no additional risk or a specific procedure to a subject and no interference between this trial and other studies