Comparing a new medication to standard treatment for preventing stomach issues in heart patients on blood thinners

A Multi-centre, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Phase 4 Efficacy and Safety Study of P-CAB (Tegoprazan 50 mg Once Daily) Compared With PPI (Rabeprazole 20 mg Once Daily) to Reduce Upper Gastrointestinal Events Including Bleeding and Symptomatic Ulcer Disease

This study is testing a new medication called tegoprazan to see if it can prevent stomach problems just as well as the standard treatment for heart patients who are taking blood thinners.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 3320 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Locations: 43 sites (Anyang and 42 other locations)
• Trial ID: NCT04416581 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of a novel potassium-competitive acid blocker (P-CAB) called tegoprazan compared to a standard proton pump inhibitor (PPI) in patients with known cardiac and vascular diseases who are at high risk for gastrointestinal bleeding due to chronic antithrombotic therapy. The study will first conduct a safety surveillance phase with 300 patients to monitor adverse events associated with tegoprazan before proceeding to a randomized, double-blind trial involving 3,100 patients. The primary goal is to determine if tegoprazan is non-inferior to the standard PPI in preventing gastrointestinal events over a 12-month period.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 and older with known cardiac and vascular diseases who are receiving chronic antithrombotic medications.

Not a fit: Patients who do not have cardiac or vascular diseases or are not on antithrombotic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer alternative for gastrointestinal protection in patients at high risk of bleeding while on antithrombotic therapy.

How similar studies have performed: Other studies have shown promising results with similar approaches, but this specific comparison of P-CAB versus PPI in this patient population is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. On the basis of clinical guidelines and expert consensus documents, we defined a study population with an 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 using of antithrombotic therapies (antiplatelet agents or OAC)
3. Concurrent use of PPI or P-CAB within 4 weeks before randomization
4. 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).
5. Baseline severe anemia (Hgb \<8 g/dl at baseline) or transfusion within 4 weeks before randomization
6. Baseline severe thrombocytopenia (platelet count \<50,000/mm3)
7. Renal failure dependent on dialysis or severe renal insufficiency (creatinine clearance \<15 ml/min)
8. Severe chronic liver disease (defined as variceal haemorrhage, ascites, hepatic encephalopathy, or jaundice)
9. Hypersensitivity or contraindication to PPI, P-CAB, any of the product components, or substituted benzimidazoles
10. Use of clarithromycin and hypersensitivity to macrolide antibiotics for Helicobacter pylori eradication
11. Concomitant use of clarithromycin with terfenadine, cisapride, astemizole, or pimozide for Helicobacter pylori eradication
12. 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)
13. Patients who take atazanavir, nelfinavir, or rilpivirine-containing products (see Drug-Drug interaction section)
14. 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
15. Any known or suspected malignancy
16. Patients with non-cardiac co-morbidities with a life expectancy of less than 12 months
17. Patients with active treatment for H-pylori infection
18. Women who are pregnant or breastfeeding or female subjects, premenopausal who are not surgically sterile, or, if sexually active not practicing 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
19. Participation in another clinical study within 12 months. However, where at least one or more conditions 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 conducted 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

Where this trial is running

Anyang and 42 other locations

• Hallym University Sacred Heart Hospital — Anyang, South Korea (Recruiting)
• Bucheon Sejong Hospital — Bucheon-si, South Korea (Recruiting)
• Kosin University Gospel Hospital — Busan, South Korea (Recruiting)
• Gyeongsang National University Changwon Hospital — Changwon, South Korea (Withdrawn)
• Sungkyunkwan University Samsung Changwon Hospital — Changwon, South Korea (Withdrawn)
• Dankook University Hospital — Cheonan, South Korea (Withdrawn)
• Chungbuk National University Hospital — Cheonju, South Korea (Recruiting)
• Gangwon National Univ. Hospital — Chuncheon, South Korea (Withdrawn)
• Hallym University Chuncheon Sacred Heart Hospital — Chuncheon, South Korea (Not_yet_recruiting)
• Keimyung University Dongsan Medical Center — Daegu, South Korea (Recruiting)
• Yeungnam University Medical Center — Daegu, South Korea (Withdrawn)
• Chungnam National University Hospital — Daejeon, South Korea (Recruiting)
• Gangneung Asan Hospital — Gangneung, South Korea (Recruiting)
• Hanyang University Guri Hospital — Guri-si, South Korea (Recruiting)
• Chonnam National University Hospital — Gwangju, South Korea (Recruiting)
• Hallym University Dongtan Sacred Heart Hospital — Hwaseong-si, South Korea (Recruiting)
• Inje University Ilsan Paik Hospital — Ilsan, South Korea (Recruiting)
• Jeonbuk National University Hospital — Jeonju, South Korea (Withdrawn)
• Kwangju Christian Hospital — Kwangju, South Korea (Withdrawn)
• Dong-A Medical Center — Pusan, South Korea (Recruiting)
• Inje University Pusan Paik Hospital — Pusan, South Korea (Recruiting)
• Pusan National University Hospital — Pusan, South Korea (Not_yet_recruiting)
• Chungnam National University Sejong Hospital — Sejong, South Korea (Recruiting)
• Bundang CHA Hospital — Seongnam, South Korea (Recruiting)
• Seoul university Bundang hospital — Seongnam-si, South Korea (Recruiting)
• Asan Medical Center — Seoul, South Korea (Recruiting)
• Chung-Ang University Hospital — Seoul, South Korea (Recruiting)
• Ewha Womans University Medical Center — Seoul, South Korea (Withdrawn)
• Hanyang University Seoul Hospital — Seoul, South Korea (Recruiting)
• Kangbuk Samsung Hospital — Seoul, South Korea (Recruiting)
• Korea University Anam Hospital — Seoul, South Korea (Recruiting)
• Kyung Hee University Hospital at Gangdong — Seoul, South Korea (Recruiting)
• Kyung Hee University Medical Center — Seoul, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)
• Severance Hospital — Seoul, South Korea (Recruiting)
• SNU Boramae Medical Center — Seoul, South Korea (Not_yet_recruiting)
• The Catholic Univ. of Korea Eunpyeong St. Mary's hospital — Seoul, South Korea (Recruiting)
• The Catholic Univ. of Korea Seoul St. Mary's hospital — Seoul, South Korea (Recruiting)
• Ajou University Hospital — Suwon, South Korea (Recruiting)
• The Catholic University of Korea, ST. Vincent's Hospital — Suwon, South Korea (Recruiting)
• Ulsan University Hospital — Ulsan, South Korea (Recruiting)
• Pusan National University Yangsan Hospital — Yangsan, South Korea (Withdrawn)
• Yonsei University Yongin Severance Hospital — Yongin-si, South Korea (Recruiting)

Study contacts

• Study coordinator: Jeong-youn Bae, RN

Conditions Coronary Artery Disease; Percutaneous Coronary Intervention; Acute Coronary Syndrome; Myocardial Infarction; gastroduodenal ulcer; gastrointestinal hemorrhage; peptic ulcer; acute coronary syndrome