Patients with ischemic stroke commonly receive antiplatelet therapy, frequently starting as dual antiplatelet therapy, which is associated with an increased risk of gastrointestinal complications. Although evidence for gastroprotection is established in coronary artery disease, no comparable guidance or evidence exists for stroke care. Tegoprazan is a potassium-competitive acid blocker offering rapid, meal-independent acid suppression with fewer drug interactions than proton pump inhibitors, yet whether it prevents such complications after stroke remains unknown. Thus, the investigators aim to evaluate whether tegoprazan reduces gastrointestinal complications in patients receiving antiplatelet therapy after ischemic stroke.

TegoStroke is a phase 3, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at more than 20 centers in the Republic of Korea. Adult patients who are starting antiplatelet therapy after acute ischemic stroke or transient ischemic attack, and who are expected to continue it for at least 6 months, will be included. Eligible patients will be 1:1 randomized to receive oral tegoprazan 50 mg once daily or matching placebo for 180 days. The primary outcome is a composite of upper or indeterminate-origin gastrointestinal bleeding, gastric or duodenal ulcer ≥3 mm, or erosive esophagitis, ascertained up to a day-180 esophagogastroduodenoscopy. This study would provide the first randomized evidence on routine gastroprotection for patients on antiplatelet therapy after ischemic stroke.

Inclusion Criteria:

1. Age 19 years or older.
2. Hospitalization for acute ischemic stroke or transient ischemic attack, with antiplatelet therapy initiated for the first time, expected to continue for at least 6 months at the treating physician's discretion per relevant stroke guidelines, and within 4 weeks of the first antiplatelet dose at the time of randomization.
3. Written informed consent provided by the participant or a legally authorized representative.
4. Ability and willingness to understand the study procedures described in the consent form and to comply with the study protocol.

Exclusion Criteria:

1. History of peptic ulcer disease diagnosis or gastrointestinal bleeding within the past year. At screening, the history and findings of any EGD performed within the preceding 2 years were obtained by participant interview.
2. Need for concomitant anticoagulant therapy (transient anticoagulation such as argatroban during the index admission is permitted, with randomization after it is stopped)
3. Anticipated difficulty in undergoing gastrointestinal endoscopy during the study period.
4. Use of a P-CAB, PPI, or H2-receptor antagonist within 1 week before randomization, or an active indication for these agents, a mucosal protectant, or an antacid at enrollment. Temporary use of these agents during acute care in the index admission, since discontinued and without a current indication, is not exclusionary.
5. Hypersensitivity or contraindication to a P-CAB or to benzimidazoles.
6. AST, ALT, ALP, or γ-GT ≥5 times the upper limit of normal (ULN), or total bilirubin ≥3 times the ULN at screening.
7. Participation within the past 12 months in any of the following: (1) a clinical study that may affect the efficacy or safety assessments of the present study; (2) a study involving an investigational product or procedure not administered under standard-of-care guidelines; (3) a study that may pose additional risk to the participant. (Participation in other clinical studies is otherwise permitted.)
8. Current use of, or use within five half-lives of, a contraindicated interacting drug (atazanavir, nelfinavir, rilpivirine, and preparations containing these components).
9. Any other condition deemed by the investigators to render the patient unsuitable for study participation, including but not limited to: