Zastaprazan for the prEvention of Upper GI Bleeding in Ischemic Stroke

Official title

A Randomized, Double-Blind, Placebo-Controlled, Multi-center, Phase 3 Clinical Trial to Evaluate the Efficacy of Zastaprazan in PrEventing Upper Gastrointestinal Bleeding in Patients With Transient Ischemic Attack or Ischemic Stroke Receiving Antiplatelet or Anticoagulant Therapy: ZEUS Trial

Overview

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)

Interventions

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

Primary outcome measures

• Time to First Composite Clinical Event of Upper Gastrointestinal Bleeding as Adjudicated by the Clinical Event Committee (CEC) [Time frame: From randomization up to end of study (up to approximately 3 years, including a 24-month enrollment period and 12-month follow-up)]

Secondary outcome measures (12)

• Time to First Composite Clinical Event of Upper Gastrointestinal Bleeding as Judged by the Investigator [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Symptomatic Gastrointestinal Erosive Lesion Event, as Adjudicated by the Clinical Event Committee (CEC) [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Upper Gastrointestinal Obstruction Event, as Adjudicated by the Clinical Event Committee (CEC) [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Upper Gastrointestinal Perforation Event, as Adjudicated by the Clinical Event Committee (CEC) [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First All Gastrointestinal Bleeding Event (Upper and Lower), Including International Society on Thrombosis and Haemostasis (ISTH) Major Bleeding or clinically relevant non-major bleeding (CRNMB) [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Lower Gastrointestinal Bleeding Event [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Non-Gastrointestinal ISTH Major Bleeding or CRNMB Event [Time frame: From randomization up to end of study (up to approximately 3 years)]
• Time to First Clinically Significant Non-Bleeding Upper Gastrointestinal Event [Time frame: From randomization up to end of study (up to approximately 3 years)]

Eligibility criteria

Inclusion criteria

• 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)

Exclusion criteria

• 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)
• History of peptic ulcer complications, including bleeding, perforation, or stricture, regardless of timing
• Active bleeding at the time of enrollment, history of a coagulation disorder, or hemodynamic instability at the time of enrollment
• Known hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Asan Medical Center — Seoul

Identifiers

NCT: NCT07730840 · ZEUS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗