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

NCT04416581 | Recruiting Phase 4 DMC

• 1 other identifier: AMCCV2020-05
• Study Type: interventional
• Target: 3,320
• Locations: 1 country
• Sites: 43

Brief Summary

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.

Conditions

Coronary Artery Disease; Percutaneous Coronary Intervention; Acute Coronary Syndrome; Myocardial Infarction

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (16)

• The event rate of overt upper gastrointestinal bleeding (confirmed by means of upper endoscopy or computed tomography)

  12 months

• The event rate of overt upper GI bleeding of unknown origin

  12 months

• 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

  12 months

• The event rate of symptomatic gastroduodenal ulcer(confirmed by means of endoscopy or computed tomography) without evidence of GI bleeding

  12 months

• The event rate of the existence of persistent pain of presumed GI origin(duration ≥ 3 days) with underlying multiple erosive diseases (5 or more gastroduodenal erosions confirmed by means of endoscopy)

  12 months

Study Arms (2)

P-CAB 50mg group

EXPERIMENTAL

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

Drug: P-CAB 50

PPI group

ACTIVE COMPARATOR

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

Drug: PPI

Interventions

PPI DRUG

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

PPI group

P-CAB 50 DRUG

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

P-CAB 50mg group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.
• History of prior GI bleeding events at any time
• History of a previously complicated ulcer
• History of peptic ulcer disease or a previously uncomplicated ulcer
• Documented Helicobacter pylori infection
• Patients who voluntarily participated in the written agreement

You may not qualify if:

• Any clinical contraindication to using of antithrombotic therapies (antiplatelet agents or OAC)
• Concurrent use of PPI or P-CAB within 4 weeks before randomization
• Baseline severe anemia (Hgb \<8 g/dl at baseline) or transfusion within 4 weeks before randomization
• Baseline severe thrombocytopenia (platelet count \<50,000/mm3)
• Renal failure dependent on dialysis or severe renal insufficiency (creatinine clearance \<15 ml/min)
• Severe chronic liver disease (defined as variceal haemorrhage, ascites, hepatic encephalopathy, or jaundice)
• Hypersensitivity or contraindication to PPI, P-CAB, any of the product components, or substituted benzimidazoles
• Use of clarithromycin and hypersensitivity to macrolide antibiotics for Helicobacter pylori eradication
• Concomitant use of clarithromycin with terfenadine, cisapride, astemizole, or pimozide for Helicobacter pylori eradication
• 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)
• Patients who take atazanavir, nelfinavir, or rilpivirine-containing products (see Drug-Drug interaction section)
• 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
• Any known or suspected malignancy
• Patients with non-cardiac co-morbidities with a life expectancy of less than 12 months
• Patients with active treatment for H-pylori infection

Sponsors & Collaborators

• Duk-Woo Park, MD: lead

Study Sites (43)

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

Related Publications (1)

• 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.

  PMID: 40188976 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Myocardial Infarction; Peptic Ulcer; Gastrointestinal Hemorrhage

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Duodenal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases; Hemorrhage

Central Study Contacts

Jeong-youn Bae, RN

CONTACT

82230107259; cvcrc10@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 4, 2020
• Study Start: May 12, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

KR (43)