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

NCT ID: NCT04416581

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

3320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-12

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Before randomization phase, one lead-in subject (N = 300 patients) will be enrolled to perform safety surveillance of standard-dose tegoprazan (50 mg for 6 months) and to ensure the safety of tegoprazan (safety surveillance phase). Data on lead-in subjects will not be included in the data set used for primary analyses.

The safety of tegoprazan will be estimated SIAEs(Special Interest Adverse Events) as follows; Composite Event

1. liver function abnormalities
2. hypergastrinemia, or
3. enteric infection

Definitions

* liver function abnormality: defined as AST or ALT\>3× upper limit of normal or two consecutive measurements of total bilirubin \>2 x upper limit of normal
* hypergastrinemia
* enteric infection including C.difficile infection

If there are any new tegoprazan-related findings, it will be considered in the estimation.

If there is no safety concern during safety surveillance phase, investigator-driven, randomized, double-blind, double-dummy, active-controlled, clinical trial (N =3,100 patients) will be subsequently performed (randomization phase).

Conditions

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Coronary Artery Disease Percutaneous Coronary Intervention Acute Coronary Syndrome Myocardial Infarction

Keywords

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gastroduodenal ulcer gastrointestinal hemorrhage peptic ulcer acute coronary syndrome coronary artery stent placement antiplatelet anticoagulant therapy PPI P-CAB Proton-pump inhibitors Potassium-Competitive Acid Blockers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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P-CAB 50mg group

tegoprazan 50 mg + rabeprazole 20mg placebo, once daily.

Group Type EXPERIMENTAL

P-CAB 50

Intervention Type DRUG

tegoprazan 50 mg + rabeprazole 20mg placebo, once daily.

PPI group

rabeprazole 20mg + tegoprazan 50 mg placebo, once daily.

Group Type ACTIVE_COMPARATOR

PPI

Intervention Type DRUG

rabeprazole 20mg + tegoprazan 50 mg placebo, once daily.

Interventions

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PPI

rabeprazole 20mg + tegoprazan 50 mg placebo, once daily.

Intervention Type DRUG

P-CAB 50

tegoprazan 50 mg + rabeprazole 20mg placebo, once daily.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duk-Woo Park, MD

OTHER

Sponsor Role lead

Responsible Party

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Duk-Woo Park, MD

Associate Professor, Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Hallym University Sacred Heart Hospital

Anyang, , South Korea

Site Status RECRUITING

Bucheon Sejong Hospital

Bucheon-si, , South Korea

Site Status RECRUITING

Kosin University Gospel Hospital

Busan, , South Korea

Site Status RECRUITING

Gyeongsang National University Changwon Hospital

Changwon, , South Korea

Site Status WITHDRAWN

Sungkyunkwan University Samsung Changwon Hospital

Changwon, , South Korea

Site Status WITHDRAWN

Dankook University Hospital

Cheonan, , South Korea

Site Status WITHDRAWN

Chungbuk National University Hospital

Cheonju, , South Korea

Site Status RECRUITING

Gangwon National Univ. Hospital

Chuncheon, , South Korea

Site Status WITHDRAWN

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, , South Korea

Site Status NOT_YET_RECRUITING

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status RECRUITING

Yeungnam University Medical Center

Daegu, , South Korea

Site Status WITHDRAWN

Chungnam National University Hospital

Daejeon, , South Korea

Site Status RECRUITING

Gangneung Asan Hospital

Gangneung, , South Korea

Site Status RECRUITING

Hanyang University Guri Hospital

Guri-si, , South Korea

Site Status RECRUITING

Chonnam National University Hospital

Gwangju, , South Korea

Site Status RECRUITING

Hallym University Dongtan Sacred Heart Hospital

Hwaseong-si, , South Korea

Site Status RECRUITING

Inje University Ilsan Paik Hospital

Ilsan, , South Korea

Site Status RECRUITING

Jeonbuk National University Hospital

Jeonju, , South Korea

Site Status WITHDRAWN

Kwangju Christian Hospital

Kwangju, , South Korea

Site Status WITHDRAWN

Dong-A Medical Center

Pusan, , South Korea

Site Status RECRUITING

Inje University Pusan Paik Hospital

Pusan, , South Korea

Site Status RECRUITING

Pusan National University Hospital

Pusan, , South Korea

Site Status NOT_YET_RECRUITING

Chungnam National University Sejong Hospital

Sejong, , South Korea

Site Status RECRUITING

Bundang CHA Hospital

Seongnam, , South Korea

Site Status RECRUITING

Seoul university Bundang hospital

Seongnam-si, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Chung-Ang University Hospital

Seoul, , South Korea

Site Status RECRUITING

Ewha Womans University Medical Center

Seoul, , South Korea

Site Status WITHDRAWN

Hanyang University Seoul Hospital

Seoul, , South Korea

Site Status RECRUITING

Kangbuk Samsung Hospital

Seoul, , South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, , South Korea

Site Status RECRUITING

Kyung Hee University Hospital at Gangdong

Seoul, , South Korea

Site Status RECRUITING

Kyung Hee University Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

SNU Boramae Medical Center

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

The Catholic Univ. of Korea Eunpyeong St. Mary's hospital

Seoul, , South Korea

Site Status RECRUITING

The Catholic Univ. of Korea Seoul St. Mary's hospital

Seoul, , South Korea

Site Status RECRUITING

Ajou University Hospital

Suwon, , South Korea

Site Status RECRUITING

The Catholic University of Korea, ST. Vincent's Hospital

Suwon, , South Korea

Site Status RECRUITING

Ulsan University Hospital

Ulsan, , South Korea

Site Status RECRUITING

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Site Status WITHDRAWN

Yonsei University Yongin Severance Hospital

Yongin-si, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Jeong-youn Bae, RN

Role: CONTACT

Phone: 82230107259

Email: [email protected]

Facility Contacts

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Sang-ho Cho, MD

Role: primary

Young-jin Choi, MD

Role: primary

Jung-ho Heo, MD

Role: primary

Sang-min Kim, MD

Role: primary

Hyun-hee Choi, MD

Role: primary

Chang-wook Nam, MD

Role: primary

Jin-ok Jeong, MD

Role: primary

Han-bit Park, MD

Role: primary

Hwan-cheol Park, MD

Role: primary

Young-joon Hong, MD

Role: primary

Jin-Hwa Lee, MD

Role: primary

Seong-wook Kwon, MD

Role: primary

Yong-rak Cho, MD

Role: primary

Tae-hyun Yang, MD

Role: primary

Han-cheol Lee, MD

Role: primary

Won-mook Hwang, MD

Role: primary

Seung-Ryul Lee, MD

Role: primary

Jung-won Suh, MD

Role: primary

Duk-woo Park, MD

Role: primary

Wang-soo Lee, MD

Role: primary

Young-hyo Lim, MD

Role: primary

Seung-Jae Lee, MD

Role: primary

Soon-jun Hong, MD

Role: primary

Eun-seon Jin, MD

Role: primary

Won Kim, MD

Role: primary

Eui-keun Choi, MD

Role: primary

Byoung-keuk Kim, MD

Role: primary

Sang-hyun Kim, MD

Role: primary

Jeong-hoon Lee, MD

Role: primary

Byung-hee Hwang, MD

Role: primary

Myoung-ho Yoon, MD

Role: primary

Sung-ho Her, MD

Role: primary

Eun-seok Shin, MD

Role: primary

Yong-Cheol Kim, MD

Role: primary

References

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Lee J, Park HS, Lee J, Choi KD, Kang DY, Ahn JM, Kim W, Lee JY, Lim YH, Kang SH, Kwon SU, Park H, Choi EK, Hong SJ, Kim BK, Jin ES, Jeong JO, Nam CW, Lee WS, Kim SM, Park KH, Her SH, Shin ES, Choi YJ, Yang TH, Kim SH, Suh JW, Park HC, Yoon YH, Yoon MH, Park SJ, Park DW; PROTECT-HBR Trial. 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. Am Heart J. 2025 Sep;287:50-60. doi: 10.1016/j.ahj.2025.04.001. Epub 2025 Apr 4.

Reference Type DERIVED
PMID: 40188976 (View on PubMed)

Other Identifiers

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AMCCV2020-05

Identifier Type: -

Identifier Source: org_study_id