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

NCT07497893 | Not Yet Recruiting

• 1 other identifier: FENOX Trial
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief 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

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

Keywords

Non-vitamin K antagonist oral anticoagulants (NOACs), potassium-competitive acid blocker (P-CAB), Upper gastrointestinal bleeding (UGIB)

Outcome Measures

Primary Outcomes (1)

• Clinically relevant upper gastrointestinal bleeding (CR-UGIB)

  Clinically relevant upper gastrointestinal bleeding (CR-UGIB) defined as either: 1. ISTH-defined major upper gastrointestinal bleeding, or 2. clinically relevant non-major upper gastrointestinal bleeding requiring emergency department visit, hospitalization, endoscopic intervention, blood transfusion, or temporary interruption of NOAC therapy. All events will be adjudicated by an independent blinded Clinical Events Committee.

  12 months

Secondary Outcomes (5)

• ISTH major bleeding

  12 months

• Intracranial hemorrhage

  12 months

• Ischemic stroke or systemic embolism

  12 months

• All-cause mortality

  12 months

• Net clinical outcome

  12 months

Other Outcomes (3)

• Adverse events

  12 months

• Serious adverse events

  12 months

• Drug discontinuation due to adverse events

  12 months

Study Arms (2)

Fexuprazan plus NOAC therapy

EXPERIMENTAL

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.

Drug: Fexuprazan; Drug: NOAC therapy

NOAC therapy alone

ACTIVE COMPARATOR

Participants will receive standard-of-care non-vitamin K antagonist oral anticoagulant (NOAC) therapy at guideline-recommended dosing without additional gastroprotective therapy.

Drug: NOAC therapy

Interventions

Fexuprazan DRUG

Fexuprazan 40 mg administered orally once daily for the duration of the study in combination with NOAC therapy.

Fexuprazan plus 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.

Fexuprazan plus NOAC therapy; NOAC therapy alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Ewha Womans University Mokdong Hospital: lead

Study Sites (1)

Ewha Womans University Mokdong Hospital

Seoul, 1071, South Korea

Location

MeSH Terms

Conditions

Atrial Fibrillation; Gastrointestinal Hemorrhage; Drug-Related Side Effects and Adverse Reactions

Interventions

fexuprazan

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Chemically-Induced Disorders

Central Study Contacts

Yeji Kim MD, PhD

CONTACT

+82-10-8680-9542; lexie6169@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: rity trial. Approximately 1,000 high-risk patients with non-valvular atrial fibrillation receiving NOAC therapy will be randomized in a 1:1 ratio to fexuprazan plus NOAC therapy or NOAC therapy alone.

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: March 27, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2032
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Access Criteria: Data will be made available to qualified researchers who provide a methodologically sound research proposal. Proposals should be directed to the corresponding author. Data access will be granted following review and approval by the study steering committee and execution of a data use agreement.

Locations

KR (1)