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

Sponsor
Ewha Womans University Mokdong Hospital
Study ID
NCT07497893
Status
Not Yet Recruiting

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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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 Dates

First listed
Mar 27, 2026
Start date
Dec 1, 2026
Status verified
Mar 2026
Primary completion
Nov 30, 2029
Completion
Nov 30, 2032

Study Design

Enrollment
1,000 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Experimental: Fexuprazan plus NOAC therapy
    Participants will receive fexuprazan 40 mg orally once daily in addition to standard-of-care non-vitamin K antagonist oral anticoagulant (NOAC) therapy at guideline-recommended dosing.
  • Active Comparator: NOAC therapy alone
    Participants will receive standard-of-care non-vitamin K antagonist oral anticoagulant (NOAC) therapy at guideline-recommended dosing without additional gastroprotective therapy.

Primary Outcome Measure

Clinically relevant upper gastrointestinal bleeding (CR-UGIB) [ Time Frame: 12 months ]

Central Contacts

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