NCT07497893

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

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

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,000 (estimated)
• Sponsor: Ewha Womans University Mokdong Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

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

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2026-12-01
• Primary completion: 2029-11-30
• Completion: 2032-11-30
• First posted: 2026-03-27
• Last updated: 2026-03-27

Locations

1 site across 1 country: South Korea