Atrial Fibrillation (AF)FENOXNCT07497893
FENOX Trial (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
A study testing Fexuprazan and NOAC therapy in people with Atrial Fibrillation (AF) and Upper Gastrointestinal Bleeding (UGIB), run by Ewha Womans University Mokdong Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation (AF), Upper Gastrointestinal Bleeding (UGIB), Gastrointestinal Hemorrhage (Clinically Important, Upper)
- What is being tested?
- Fexuprazan and NOAC therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Dec 2026to 30 Nov 2032
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site
Ewha Womans University Mokdong Hospital
Seoul, 1071
Junbeom Park, PhD, +82-02-3539-9822, newriser@naver.com
About this study
Official title: FENOX Study (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
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.
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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
- Being tested
- Fexuprazan, NOAC therapy
- Keywords
- Non-vitamin K antagonist oral anticoagulants (NOACs), potassium-competitive acid blocker (P-CAB), Upper gastrointestinal bleeding (UGIB)
- Medical subject headings
- Atrial Fibrillation, Gastrointestinal Hemorrhage, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FexuprazanDrug
Fexuprazan 40 mg administered orally once daily for the duration of the study in combination with NOAC therapy.
NOAC therapyDrug
Non-vitamin K antagonist oral anticoagulant therapy (e.g., apixaban, rivaroxaban, dabigatran, or edoxaban) administered according to approved labeling and guideline-recommended dosing.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: NOAC therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinically relevant upper gastrointestinal bleeding (CR-UGIB)
Clinically relevant upper gastrointestinal bleeding (CR-UGIB) defined as either:
- ISTH-defined major upper gastrointestinal bleeding, or
- 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.
Measured: 12 months
Secondary outcomes (5)
ISTH major bleeding
Major bleeding defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria.
Measured: 12 months
Intracranial hemorrhage
Occurrence of intracranial hemorrhage confirmed by neuroimaging or clinical diagnosis.
Measured: 12 months
Ischemic stroke or systemic embolism
Composite of ischemic stroke or systemic embolism confirmed by clinical and imaging criteria.
Measured: 12 months
All-cause mortality
Death from any cause during the follow-up period.
Measured: 12 months
Net clinical outcome
Composite of clinically relevant upper gastrointestinal bleeding, ischemic stroke/systemic embolism, intracranial hemorrhage, or all-cause death.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start1 Dec 2026 (estimated)
- Primary completion30 Nov 2029 (estimated)
- Study completion30 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial Fibrillation (AF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ewha Womans University Mokdong Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07497893
- Sponsor's protocol ID
- FENOX Trial
- Acronym
- FENOX
- Status last verified
- Mar 2026
- First submitted
- 23 Mar 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) that underlie the results reported in this study, after de-identification, will be shared.