FENOX Trial (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)

Официальное название

FENOX Study (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)

Обзор

Background Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (AF). Although NOACs substantially reduce intracranial hemorrhage, upper gastrointestinal bleeding (UGIB) remains a frequent and clinically consequential complication. Proton pump inhibitors (PPIs) may reduce UGIB risk; however, concerns regarding long-term safety and pharmacodynamic variability persist. Fexuprazan, a potassium-competitive acid blocker (P-CAB), provides rapid and sustained acid suppression independent of acid activation and CYP2C19 metabolism. No randomized trial has evaluated P-CAB therapy for prevention of UGIB in anticoagulated patients. Methods FENOX is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) superiority trial. Approximately 1,000 high-risk patients with non-valvular AF initiating NOAC therapy will be randomized 1:1 to receive fexuprazan plus NOAC therapy or NOAC therapy alone. High-risk enrichment includes advanced age, renal impairment, concomitant antiplatelet therapy, prior ulcer disease, or elevated HAS-BLED score. The primary endpoint is clinically relevant upper gastrointestinal bleeding (CR-UGIB) at 12 months, defined according to ISTH criteria. All events will be adjudicated by an independent blinded Clinical Events Committee. Primary analyses will follow the intention-to-treat principle using time-to-event methods. Results The planned sample size provides 80% power to detect a 50% relative risk reduction in CR-UGIB, assuming a 12-month incidence of 10% in the control group. Interim safety monitoring will be conducted under independent oversight. Conclusion FENOX is the first randomized trial designed to evaluate a P-CAB-based gastroprotective strategy for prevention of clinically relevant UGIB in high-risk patients receiving NOAC therapy. By integrating high-risk enrichment, pragmatic design, and blinded endpoint adjudication, the study aims to provide rigorous evidence to inform gastroprotective strategies in anticoagulated populations.

Вмешательства

• Препарат Fexuprazan
  Fexuprazan 40 mg administered orally once daily for the duration of the study in combination with NOAC therapy.
• Препарат NOAC therapy
  Non-vitamin K antagonist oral anticoagulant therapy (e.g., apixaban, rivaroxaban, dabigatran, or edoxaban) administered according to approved labeling and guideline-recommended dosing.

Первичные конечные точки

• Clinically relevant upper gastrointestinal bleeding (CR-UGIB) [Срок оценки: 12 months]

Вторичные конечные точки (5)

• ISTH major bleeding [Срок оценки: 12 months]
• Intracranial hemorrhage [Срок оценки: 12 months]
• Ischemic stroke or systemic embolism [Срок оценки: 12 months]
• All-cause mortality [Срок оценки: 12 months]
• Net clinical outcome [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age ≥18 years
• Documented non-valvular atrial fibrillation
• Receiving or initiating therapy with a non-vitamin K antagonist oral anticoagulant (NOAC) at guideline-recommended dosing
• At least one high-risk factor for upper gastrointestinal bleeding, including:

• Age ≥75 years
• Chronic kidney disease (eGFR <60 mL/min/1.73 m²)
• Concomitant antiplatelet therapy
• Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids
• Prior peptic ulcer disease or upper gastrointestinal bleeding
• HAS-BLED score ≥3

Критерии исключения

• Active gastrointestinal bleeding at the time of screening
• Requirement for mandatory long-term proton pump inhibitor (PPI) therapy that cannot be discontinued
• Severe hepatic dysfunction
• Life expectancy <1 year
• Known hypersensitivity or contraindication to fexuprazan
• Participation in another interventional clinical trial that may interfere with study outcomes

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

South Korea · 1 центр

• Ewha Womans University Mokdong Hospital — Seoul

Идентификаторы

NCT: NCT07497893 · FENOX Trial

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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