FENOX Trial (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Fexuprazan, NOAC therapy.
- Who it may be relevant to
- Registry conditions: Atrial Fibrillation (AF), Upper Gastrointestinal Bleeding (UGIB), Gastrointestinal Hemorrhage (Clinically Important, Upper), Drug-Related Side Effects and Adverse Reactions. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- South Korea
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
FENOX Study (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
Overview
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.
Interventions
- Drug Fexuprazan
Fexuprazan 40 mg administered orally once daily for the duration of the study in combination with NOAC therapy. - Drug 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.
Primary outcome measures
- Clinically relevant upper gastrointestinal bleeding (CR-UGIB) [Time frame: 12 months]
Secondary outcome measures (5)
- ISTH major bleeding [Time frame: 12 months]
- Intracranial hemorrhage [Time frame: 12 months]
- Ischemic stroke or systemic embolism [Time frame: 12 months]
- All-cause mortality [Time frame: 12 months]
- Net clinical outcome [Time frame: 12 months]
Eligibility criteria
Inclusion criteria
- 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 criteria
- 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
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
- Open label
- Primary purpose
- Prevention
Study locations
South Korea · 1 center
- Ewha Womans University Mokdong Hospital — Seoul
Identifiers
NCT: NCT07497893 · FENOX Trial