Tegoprazan for Prevention of Gastrointestinal Complication in Ischemic Stroke Patients on Antiplatelet Therapy (TegoStroke)

Official title

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Superiority, Investigator-initiated Trial of Tegoprazan for Prevention of Gastrointestinal Complication in Ischemic Stroke Patients on Antiplatelet Therapy (TegoStroke)

Overview

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.

Interventions

• Drug Tegoprazan 50 mg
  Tegoprazan 50mg daily + Antiplatelet therapy
• Drug Placebo
  Placebo drug + Antiplatelet therapy

Primary outcome measures

• Composite gastrointestinal complication [Time frame: 180 days]

Secondary outcome measures (9)

• Upper GI bleeding [Time frame: 180 days]
• GI bleeding of unknown upper/lower origin [Time frame: 180 days]
• Gastric ulcer [Time frame: 180 days]
• Duodenal ulcer [Time frame: 180 days]
• Erosive esophagitis severity [Time frame: 180 days]
• Gastric mucosal injury [Time frame: 180 days]
• Gastrointestinal Symptom Rating Scale score [Time frame: 180 days]
• Change of Reflux Disease Questionnaire (RDQ) score [Time frame: 180 days]
• GI symptoms requiring medication [Time frame: 180 days]

Eligibility criteria

Inclusion criteria

• Age 19 years or older.
• 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.
• Written informed consent provided by the participant or a legally authorized representative.
• Ability and willingness to understand the study procedures described in the consent form and to comply with the study protocol.

Exclusion criteria

• 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.
• Need for concomitant anticoagulant therapy (transient anticoagulation such as argatroban during the index admission is permitted, with randomization after it is stopped)
• Anticipated difficulty in undergoing gastrointestinal endoscopy during the study period.
• 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.
• Hypersensitivity or contraindication to a P-CAB or to benzimidazoles.
• AST, ALT, ALP, or γ-GT ≥5 times the upper limit of normal (ULN), or total bilirubin ≥3 times the ULN at screening.
• 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.)
• Current use of, or use within five half-lives of, a contraindicated interacting drug (atazanavir, nelfinavir, rilpivirine, and preparations containing these components).
• Any other condition deemed by the investigators to render the patient unsuitable for study participation, including but not limited to:

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

Triple blind

Primary purpose

Prevention

Study locations

South Korea · 24 centers

• Pusan National University Hospital — Busan
• Keimyung University Dongsan Hospital — Daegu
• Hallym University Chuncheon Sacred Heart Hospital — Chuncheon
• Kangwon National University Hospital — Chuncheon
• Hallym University Sacred Heart Hospital — Anyang-si
• Wonkwang University Hospital — Iksan
• Jeonbuk National University Hospital — Jeonju
• Chungbuk National University Hospital — Cheongju-si
• … and 16 more centers

Publications

• Kim SH, Cho KB, Chun HJ, Lee SW, Kwon JG, Lee DH, Kim SG, Jung HY, Kim JW, Lee JS, Park H, Choi SC, Jee SR, Kim HS, Ko KH, Park SJ, Lee YC, Park SH, Kim AR, Kim EJ, Park HW, Kim BT, Song GS. Randomised clinical trial: comparison of tegoprazan and placebo in non-erosive reflux disease. Aliment Pharmacol Ther. 2021 Aug;54(4):402-411. doi: 10.1111/apt.16477. Epub 2021 Jul 6. PMID 34227708
• Cho YK, Choi MG, Choi SC, Lee KM, Kim TO, Park SH, Moon JS, Lim YJ, Kang DH, Cheon GJ, Baik GH, Kim KO, Cho KB, Jang JS, Park JJ, Son BK, Jung HK, Kim BW, Kim SK, Lee ST, Cha JM, Kim AR, Kim EJ, Park HW, Song GS. Randomised clinical trial: tegoprazan, a novel potassium-competitive acid blocker, or lansoprazole in the treatment of gastric ulcer. Aliment Pharmacol Ther. 2020 Sep;52(5):789-797. doi: PMID 32701188
• Sugano K, Choi MG, Lin JT, Goto S, Okada Y, Kinoshita Y, Miwa H, Chiang CE, Chiba T, Hori M, Fukushima Y, Kim HS, Chang CY, Date M; LAVENDER Study Group. Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study. Gut. 2014 Jul;63(7):1061-8. doi: 10.1136/gutjnl PMID 24326741
• Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Ass PMID 34024117
• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the mana PMID 39210710
• Yeomans N, Lanas A, Labenz J, van Zanten SV, van Rensburg C, Racz I, Tchernev K, Karamanolis D, Roda E, Hawkey C, Naucler E, Svedberg LE. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol. 2008 Oct;103(10):2465-73. doi: 10.1111/j.1572-0241.2008.01995.x. Epub 2008 Jul 12. PMID 18637091
• Taha AS, McCloskey C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial. Lancet. 2009 Jul 11;374(9684):119-25. doi: 10.1016/S0140-6736(09)61246-0. Epub 2009 Jul 3. PMID 19577798
• Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, Shook TL, Lapuerta P, Goldsmith MA, Laine L, Scirica BM, Murphy SA, Cannon CP; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010 Nov 11;363(20):1909-17. doi: 10.1056/NEJMoa1007964. Epub 2010 Oct 6. PMID 20925534

Identifiers

NCT: NCT07687706 · TEGOSTROKE-P3-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗