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
- Are there results?
- Not yet: the study is under way
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.
Read more
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.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FENOX Study (Comparative Effectiveness of Fexuprazan Co-therapy in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulants)
- ClinicalTrials.gov ID
- NCT07497893
- Acronym / sponsor ID
- FENOX / FENOX Trial
- Conditions
- Atrial Fibrillation (AF), Upper Gastrointestinal Bleeding (UGIB), Gastrointestinal Hemorrhage (Clinically Important, Upper), Drug-Related Side Effects and Adverse Reactions
- Keywords
- Non-vitamin K antagonist oral anticoagulants (NOACs), potassium-competitive acid blocker (P-CAB), Upper gastrointestinal bleeding (UGIB)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Ewha Womans University Mokdong HospitalUniversity, hospital or other
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 30 Nov 2029 (estimated)
- Study completion
- 30 Nov 2032 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Fexuprazan plus NOAC therapy | Experimental | Drug: Fexuprazan, Drug: NOAC therapyParticipants 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. |
| NOAC therapy alone | Active comparator | Drug: NOAC therapyParticipants will receive standard-of-care non-vitamin K antagonist oral anticoagulant (NOAC) therapy at guideline-recommended dosing without additional gastroprotective therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FexuprazanFexuprazan 40 mg administered orally once daily for the duration of the study in combination with NOAC therapy. | Drug | Fexuprazan plus NOAC therapy |
| NOAC therapyNon-vitamin K antagonist oral anticoagulant therapy (e.g., apixaban, rivaroxaban, dabigatran, or edoxaban) administered according to approved labeling and guideline-recommended dosing. | Drug | Fexuprazan plus NOAC therapy, NOAC therapy alone |
Primary outcome
Clinically relevant upper gastrointestinal bleeding (CR-UGIB)
Time frame: 12 months
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.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) that underlie the results reported in this study, after de-identification, will be shared.
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ATRIAL APPENDAGE CLOSURE for ATRIAL FIBRILLATION, Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yeji Kim MD, PhD (+82-10-8680-9542, lexie6169@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically relevant upper gastrointestinal bleeding (CR-UGIB) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.