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

Starting soon · Not applicable

Conditions studied: Atrial Fibrillation (AF), Upper Gastrointestinal Bleeding (UGIB), Gastrointestinal Hemorrhage (Clinically Important, Upper), Drug-Related Side Effects and Adverse Reactions

In brief

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.

Key facts

Study ID

NCT07497893

Run by

Ewha Womans University Mokdong Hospital

People needed

1000

Starts

2026-12-01

Expected to finish

2032-11-30

Last updated by the study team

2026-03-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• Ewha Womans University Mokdong Hospital — Seoul, South Korea

Full record on ClinicalTrials.gov

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