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

December 23, 2025 updated by: Duk-Woo Park, MD

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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).

Study Type

Interventional

Enrollment (Estimated)

3320

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • South Korea
      • Anyang, South Korea
        • Recruiting
        • Hallym University Sacred Heart Hospital
        • Contact:
          • Sang-ho Cho, MD
        • Principal Investigator:
          • Sang-ho Cho, MD
      • Bucheon-si, South Korea
        • Recruiting
        • Bucheon Sejong Hospital
        • Contact:
          • Young-jin Choi, MD
        • Principal Investigator:
          • Young-jin Choi, MD
      • Busan, South Korea
        • Recruiting
        • Kosin University Gospel Hospital
        • Contact:
          • Jung-ho Heo, MD
        • Principal Investigator:
          • Jung-ho Heo, MD
      • Changwon, South Korea
        • Withdrawn
        • Gyeongsang National University Changwon Hospital
      • Changwon, South Korea
        • Withdrawn
        • Sungkyunkwan University Samsung Changwon Hospital
      • Cheonan, South Korea
        • Withdrawn
        • Dankook University Hospital
      • Cheonju, South Korea
        • Recruiting
        • Chungbuk National University Hospital
        • Contact:
          • Sang-min Kim, MD
        • Principal Investigator:
          • Sang-min Kim, MD
      • Chuncheon, South Korea
        • Withdrawn
        • Gangwon National Univ. Hospital
      • Chuncheon, South Korea
        • Not yet recruiting
        • Hallym University Chuncheon Sacred Heart Hospital
        • Contact:
          • Hyun-hee Choi, MD
        • Principal Investigator:
          • Hyun-hee Choi, MD
      • Daegu, South Korea
        • Recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:
          • Chang-wook Nam, MD
        • Principal Investigator:
          • Chang-wook Nam, MD
      • Daegu, South Korea
        • Withdrawn
        • Yeungnam University Medical Center
      • Daejeon, South Korea
        • Recruiting
        • Chungnam National University Hospital
        • Contact:
          • Jin-ok Jeong, MD
        • Principal Investigator:
          • Jin-ok Jeong, MD
      • Gangneung, South Korea
        • Recruiting
        • GangNeung Asan Hospital
        • Contact:
          • Han-bit Park, MD
        • Principal Investigator:
          • Han-bit Park, MD
      • Guri-si, South Korea
        • Recruiting
        • Hanyang University Guri Hospital
        • Contact:
          • Hwan-cheol Park, MD
        • Principal Investigator:
          • Hwan-cheol Park, MD
      • Gwangju, South Korea
        • Recruiting
        • Chonnam National University Hospital
        • Contact:
          • Young-joon Hong, MD
        • Principal Investigator:
          • Young-joon Hong, MD
      • Hwaseong-si, South Korea
        • Recruiting
        • Hallym University Dongtan Sacred Heart Hospital
        • Principal Investigator:
          • Jin-Hwa Lee, MD
        • Contact:
          • Jin-Hwa Lee, MD
      • Ilsan, South Korea
        • Recruiting
        • Inje University Ilsan Paik Hospital
        • Contact:
          • Seong-wook Kwon, MD
        • Principal Investigator:
          • Seong-wook Kwon, MD
      • Jeonju, South Korea
        • Withdrawn
        • Jeonbuk National University Hospital
      • Kwangju, South Korea
        • Withdrawn
        • Kwangju Christian hospital
      • Pusan, South Korea
        • Recruiting
        • Dong-A Medical Center
        • Principal Investigator:
          • Yong-rak Cho, MD
        • Contact:
          • Yong-rak Cho, MD
      • Pusan, South Korea
        • Recruiting
        • Inje University Pusan Paik Hospital
        • Contact:
          • Tae-hyun Yang, MD
        • Principal Investigator:
          • Tae-hyun Yang, MD
      • Pusan, South Korea
        • Not yet recruiting
        • Pusan National University Hospital
        • Contact:
          • Han-cheol Lee, MD
        • Principal Investigator:
          • Han-cheol Lee, MD
      • Sejong, South Korea
        • Recruiting
        • Chungnam National University Sejong Hospital
        • Contact:
          • Won-mook Hwang, MD
        • Principal Investigator:
          • Won-mook Hwang, MD
      • Seongnam, South Korea
        • Recruiting
        • Bundang CHA Hospital
        • Contact:
          • Seung-Ryul Lee, MD
        • Principal Investigator:
          • Seung-Ryul Lee, MD
      • Seongnam-si, South Korea
        • Recruiting
        • Seoul university Bundang hospital
        • Principal Investigator:
          • Jung-won Suh, MD
        • Contact:
          • Jung-won Suh, MD
      • Seoul, South Korea
        • Recruiting
        • Chung-Ang University Hospital
        • Contact:
          • Wang-soo Lee, MD
        • Principal Investigator:
          • Wang-soo Lee, MD
      • Seoul, South Korea
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Eui-keun Choi, MD
        • Principal Investigator:
          • Eui-keun Choi, MD
      • Seoul, South Korea
        • Recruiting
        • Asan Medical Center
        • Contact:
        • Principal Investigator:
          • Duk-woo Park, MD
      • Seoul, South Korea
        • Recruiting
        • Severance Hospital
        • Contact:
          • Byoung-keuk Kim, MD
        • Principal Investigator:
          • Byoung-keuk Kim, MD
      • Seoul, South Korea
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
          • Soon-jun Hong, MD
        • Principal Investigator:
          • Soon-jun Hong, MD
      • Seoul, South Korea
        • Recruiting
        • Kangbuk Samsung Hospital
        • Contact:
          • Seung-Jae Lee, MD
        • Principal Investigator:
          • Seung-Jae Lee, MD
      • Seoul, South Korea
        • Recruiting
        • Hanyang University Seoul Hospital
        • Contact:
          • Young-hyo Lim, MD
        • Principal Investigator:
          • Young-hyo Lim, MD
      • Seoul, South Korea
        • Recruiting
        • The Catholic Univ. of Korea Eunpyeong St. Mary's Hospital
        • Contact:
          • Jeong-hoon Lee, MD
        • Principal Investigator:
          • Jeong-hoon Lee, MD
      • Seoul, South Korea
        • Recruiting
        • Kyung Hee University Hospital at Gangdong
        • Contact:
          • Eun-seon Jin, MD
        • Principal Investigator:
          • Eun-seon Jin, MD
      • Seoul, South Korea
        • Not yet recruiting
        • SNU Boramae Medical Center
        • Contact:
          • Sang-hyun Kim, MD
        • Principal Investigator:
          • Sang-hyun Kim, MD
      • Seoul, South Korea
        • Withdrawn
        • Ewha Womans University Medical Center
      • Seoul, South Korea
        • Recruiting
        • Kyung Hee University Medical Center
        • Contact:
          • Won Kim, MD
        • Principal Investigator:
          • Won Kim, MD
      • Seoul, South Korea
        • Recruiting
        • The Catholic Univ. of Korea Seoul St. Mary's Hospital
        • Contact:
          • Byung-hee Hwang, MD
        • Principal Investigator:
          • Byung-hee Hwang, MD
      • Suwon, South Korea
        • Recruiting
        • Ajou University Hospital
        • Contact:
          • Myoung-ho Yoon, MD
        • Principal Investigator:
          • Myoung-ho Yoon, MD
      • Suwon, South Korea
        • Recruiting
        • The Catholic University of Korea, St. Vincent's Hospital
        • Contact:
          • Sung-ho Her, MD
        • Principal Investigator:
          • Sung-ho Her, MD
      • Ulsan, South Korea
        • Recruiting
        • Ulsan University Hospital
        • Contact:
          • Eun-seok Shin, MD
        • Principal Investigator:
          • Eun-seok Shin, MD
      • Yangsan, South Korea
        • Withdrawn
        • Pusan National University Yangsan Hospital
      • Yongin-si, South Korea
        • Recruiting
        • Yonsei University Yongin Severance Hospital
        • Contact:
          • Yong-Cheol Kim, MD
        • Principal Investigator:
          • Yong-Cheol Kim, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: P-CAB 50mg group
tegoprazan 50 mg + rabeprazole 20mg placebo, once daily.
Drug: P-CAB 50
tegoprazan 50 mg + rabeprazole 20mg placebo, once daily.
Active Comparator: PPI group
rabeprazole 20mg + tegoprazan 50 mg placebo, once daily.
Drug: PPI
rabeprazole 20mg + tegoprazan 50 mg placebo, once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The time from randomization to the first occurrence of a composite endpoint of upper GI clinical events, including during the treatment period
Time Frame: 12 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The event rate of overt upper gastrointestinal bleeding (confirmed by means of upper endoscopy or computed tomography)
Time Frame: 12 months
12 months
The event rate of overt upper GI bleeding of unknown origin
Time Frame: 12 months
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
Time Frame: 12 months
12 months
The event rate of symptomatic gastroduodenal ulcer(confirmed by means of endoscopy or computed tomography) without evidence of GI bleeding
Time Frame: 12 months
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)
Time Frame: 12 months
12 months
The event rate of gastrointestinal obstruction
Time Frame: 12 months
12 months
The event rate of gastrointestinal perforation
Time Frame: 12 months
12 months
The time from randomization to discontinuation of study medication attributed to gastrointestinal signs or symptoms
Time Frame: 12 months
12 months
The event rate of gastroesophageal reflux disease, as evidenced by symptomatic endoscopically confirmed erosive esophagitis
Time Frame: 12 months
12 months
The event rate of composite cardiovascular safety endpoints
Time Frame: 12 months

composite cardiovascular safety endpoints including:

  1. death from cardiovascular causes;
  2. myocardial infarction; or
  3. stroke

A composite endpoint is an endpoint that is a combination of multiple clinical endpoints. An event that is considered to have occurred if any one of several different events is observed.
12 months
The event rate of death from cardiovascular causes
Time Frame: 12 months
12 months
The event rate of myocardial infarction
Time Frame: 12 months
12 months
The event rate of stroke
Time Frame: 12 months
12 months
The event rate of any coronary or peripheral revascularization
Time Frame: 12 months
12 months
The event rate of all-cause mortality
Time Frame: 12 months
12 months
The event rate of any possible side effect of proton pump inhibitor (PPI) or Potassium-competitive acid blocker (PCAB)
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duk-Woo Park, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 12, 2021

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

May 28, 2020

First Submitted That Met QC Criteria

June 1, 2020

First Posted (Actual)

June 4, 2020

Study Record Updates

Last Update Posted (Actual)

December 30, 2025

Last Update Submitted That Met QC Criteria

December 23, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMCCV2020-05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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