Zastaprazan for the prEvention of Upper GI Bleeding in Ischemic Stroke

NCT07730840 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: ZEUS
• Study Type: interventional
• Target: 984
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if zastaprazan can help prevent upper gastrointestinal bleeding in adults who have recently had a transient ischemic attack (TIA) or ischemic stroke and are taking antiplatelet or anticoagulant medications. The main question it aims to answer is: \- Does zastaprazan reduce the risk of upper gastrointestinal bleeding compared to placebo in these patients? Researchers will compare zastaprazan to a placebo (a look-alike tablet that contains no drug) to see if zastaprazan works to prevent upper gastrointestinal bleeding. Participants will:

• Take zastaprazan (20 mg) or a placebo once daily for the duration of the study, in addition to their prescribed antiplatelet or anticoagulant medication
• Visit the study site regularly for safety monitoring, including vital signs, physical exams, and laboratory tests
• Be monitored for any signs of gastrointestinal bleeding or other adverse events for up to approximately 3 years (including screening, treatment, and follow-up periods)

Conditions

Ischemic Stroke; Transient Ischemic Attack

Outcome Measures

Primary Outcomes (1)

• Time to First Composite Clinical Event of Upper Gastrointestinal Bleeding as Adjudicated by the Clinical Event Committee (CEC)

  Time from randomization to the first occurrence of a composite clinical event of upper gastrointestinal (GI) bleeding, as adjudicated by the Clinical Event Committee (CEC). The composite event includes: (1) upper GI bleeding confirmed by endoscopy or imaging, with hematemesis and/or melena; (2) upper GI bleeding of unclear origin, judged by the investigator to originate from the upper GI tract; (3) occult GI bleeding, defined as a decrease in hemoglobin ≥2 g/dL or hematocrit ≥10%; (4) symptomatic uncomplicated gastroduodenal ulcer, confirmed by endoscopy or imaging with persistent pain (≥3 days) and no evidence of bleeding; (5) symptomatic gastroduodenal erosive lesions, with persistent pain (≥3 days) and ≥5 gastroduodenal erosions confirmed by endoscopy, excluding mucosal bleeding; (6) upper GI obstruction; and (7) upper GI perforation.

  From randomization up to end of study (up to approximately 3 years, including a 24-month enrollment period and 12-month follow-up)

Secondary Outcomes (15)

• Time to First Composite Clinical Event of Upper Gastrointestinal Bleeding as Judged by the Investigator

  From randomization up to end of study (up to approximately 3 years)

• Time to First Upper Gastrointestinal Bleeding Event Confirmed by Endoscopy or Imaging, as Adjudicated by the Clinical Event Committee (CEC)

  From randomization up to end of study (up to approximately 3 years)

• Time to First Upper Gastrointestinal Bleeding Event of Unclear Origin, as Adjudicated by the Clinical Event Committee (CEC)

  From randomization up to end of study (up to approximately 3 years)

• Time to First Occult Gastrointestinal Bleeding Event, as Adjudicated by the Clinical Event Committee (CEC)

  From randomization up to end of study (up to approximately 3 years)

• Time to First Symptomatic Uncomplicated Gastroduodenal Ulcer Event, as Adjudicated by the Clinical Event Committee (CEC)

  From randomization up to end of study (up to approximately 3 years)

Other Outcomes (1)

• Subgroup Analyses of the Primary Composite Upper Gastrointestinal Bleeding Event

  From randomization up to end of study (up to approximately 3 years)

Study Arms (2)

Zastaprazan

EXPERIMENTAL

Participants will receive zastaprazan citrate 20 mg, administered orally once daily (QD) at a fixed dose, in addition to their prescribed antiplatelet therapy (dual antiplatelet therapy) or oral anticoagulant therapy (NOAC or warfarin).

Drug: Zastaprazan

Placebo

PLACEBO COMPARATOR

Participants will receive a matching placebo for zastaprazan 20 mg, administered orally once daily (QD) at a fixed dose, in addition to their prescribed antiplatelet therapy (dual antiplatelet therapy) or oral anticoagulant therapy (NOAC or warfarin).

Drug: Placebo

Interventions

Zastaprazan DRUG

Zastaprazan citrate 20 mg, a potassium-competitive acid blocker (P-CAB), administered orally once daily at a fixed dose, in addition to standard antiplatelet or anticoagulant therapy.

Zastaprazan

Placebo DRUG

Matching placebo for zastaprazan citrate 20 mg, administered orally once daily at a fixed dose, in addition to standard antiplatelet or anticoagulant therapy.

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults aged 19 years or older
• Onset of transient ischemic attack (TIA) or ischemic stroke within 180 days prior to randomization
• Currently initiating or receiving, at the time of randomization, one of the following treatments, with an expected treatment duration of at least 3 weeks:
• A. Dual antiplatelet therapy (DAPT) - aspirin in combination with one of the following: clopidogrel, ticagrelor, prasugrel, or cilostazol B. Oral anticoagulant therapy - a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) or warfarin
• Provision of written informed consent by the participant (or legally authorized representative)

You may not qualify if:

• Clinically significant peptic ulcer or gastrointestinal bleeding within 1 year prior to enrollment
• Moderate to severe hepatic impairment (e.g., diagnosis of cirrhosis or confirmed esophageal/gastric varices)
• Severe thrombocytopenia (platelet count \<50,000/µL)
• End-stage renal disease requiring dialysis, or unstable renal function precluding safe anticoagulant dose adjustment (eGFR \<15 mL/min/1.73m²)
• Known hypersensitivity to potassium-competitive acid blockers (P-CABs) or to the investigational product
• History of major gastrointestinal surgery resulting in malabsorption, bowel obstruction, or inability to take oral medication
• History of osteoporotic fracture or fragility fracture
• Diagnosis of a condition requiring long-term, high-dose systemic corticosteroid therapy
• Diagnosis of a condition requiring long-term concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs)
• Pregnant or breastfeeding women
• Life expectancy of less than 6 months due to pre-existing comorbid conditions
• Current participation in another interventional clinical trial that could affect the results of this study
• Any condition that, in the investigator's judgment, precludes participation
• Participant or partner of childbearing/reproductive potential who does not agree to use a medically acceptable method of contraception, or to abstain from sexual activity with risk of pregnancy, during the study period
• Currently receiving, or having received within 5 half-lives prior to randomization, a prohibited concomitant medication expected to interact with the investigational product (products containing atazanavir, nelfinavir, or rilpivirine)

Sponsors & Collaborators

• Asan Medical Center: lead
• Jeil Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Ischemic Stroke; Ischemic Attack, Transient

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia

Study Officials

• Bum Joon Kim, Ph.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bum Joon Kim, MD, Ph.D.

CONTACT

+82-2- 3010-3981; bj.kim@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 28, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)