Fexuprazan to Prevent Stomach Bleeding in People Taking Blood Thinners for Atrial Fibrillation
Tests fexuprazan added to blood thinners in adults with atrial fibrillation.
Plain-language title generated from the registry record
Registry title: FENOX Trial (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
Key facts
- Where
- Seoul, South KoreaSee the site
Where in South Korea
- Ewha Womans University Mokdong HospitalSeoul, South KoreaNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Ewha Womans University Mokdong Hospital
- Trial code
- NCT07497893
- Record updated
- 27 March 2026
- Original description
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.Read full original descriptionShow less
FENOX Study (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
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.
Inclusion: 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.
Exclusion: Requirement for mandatory long-term proton pump inhibitor (PPI) therapy that cannot be discontinued; Active gastrointestinal bleeding at the time of screening; Known hypersensitivity or contraindication to fexuprazan; Severe hepatic dysfunction; Life expectancy <1 year; Participation in another interventional clinical trial that may interfere with study outcomes.