The Incidence of New-brain Lesions on Brain MRI and Safety Between Edoxaban and Apixaban in Patients with Stroke and Nonvalvular Atrial Fibrillation (APIXABAN)

A Randomized, Open-label, Investigator-led, Pilot Trial Investigating the Incidence of New-brain Lesions on Brain MRI and Safety Between Edoxaban and Apixaban in Patients with Stroke and Nonvalvular Atrial Fibrillation

This study aims to determine whether there is a difference in brain lesion occurrence and safety when brain MRI is followed up between edoxaban and apixaban in stroke patients with nonvalvular atrial fibrillation through exploratory clinical trials.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Drug: Administration of Apixaban; Drug: Administration of Edoxaban

Detailed Description

This study is a prospective open randomized clinical trial that can confirm which group the subject was assigned to.After randomization, either the test group or the control group is prescribed, and the outcome variable is checked at 24 months. Therefore, patients who were previously administering edoxaban and apixaban can participate in the study, but if a patient who is administering edoxaban is assigned to apixaban, the drug is taken as apixaban, and similarly, if a patient who is administering apixaban is assigned to an edoxaban, the drug is changed to edoxaban and taken. During clinical trials, testers and researchers carefully observe the occurrence of adverse reactions during the follow-up period after randomization, and closely observe outcome variables, including neurological changes. During the clinical trial period, visits are made after 6, 12, 18, and 24 months, respectively, to check the signs of physical vitality, drug history, side effects, and other research-related events, and brain MR is performed at the 24th month to check the effectiveness and safety. Brain MR can be performed for various reasons before 24 months.In the brain image performed 24 months ago, if the drug is changed or stopped for a long time, the tester plans to first implement appropriate medical measures and then determine whether to continue this study. This clinical trial is a prospective open study and will be conducted in compliance with the usual diagnosis and treatment process, and in particular, all subjects will be properly tested and treated in accordance with the standard treatment guidelines for ischemic stroke during the clinical trial.

Subjects may receive active treatment according to the standard treatment guidelines for ischemic stroke during the clinical trial. In stroke patients with nonvalvular atrial fibrillation, NOAC administration is itself a standard practice guideline, so participating in this study does not deviate from the standard treatment guidelines for stroke at all. In principle, when all planned visits are completed, the subject's participation in the clinical trial will be terminated.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sujin Han Clinical Research Coordinator; Phone Number: 82-2-6986-2635; Email: sujinhan1004@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 07804
    • Ewha Womans University Medical Center
    • Contact: Tae Jin Song, MD; Phone Number: 82269863307; Email: knstar@ewha.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 19 or over.
2. Patients who are neurologically stable 14 days after diagnosis of ischemic stroke and who have undergone brain MRI (including MR diffusion, FLAIR, and GRE sequence) at diagnosis of ischemic stroke (In general, the patient's condition stabilizes within seven days of acute cerebral infarction, but cerebral infarction with atrial fibrillation is more frequent than patients without atrial fibrillation, so we want to target patients with neurological stability after 14 days. Most NOAC-related clinical trials were conducted when the patient's condition became neurologically stable at least two weeks after the stroke.)
3. Patients with atrial fibrillation confirmed by 12-lead electrocardiogram or Holter's examination for more than 24 hours and nonvalvular atrial fibrillation
4. A person who voluntarily agrees to participate in this clinical trial in writing

Exclusion Criteria:

1. Patients unable or contraindicated to administer anticoagulants and antithrombotic agents
2. Patients with less than 80,000 platelets, less than 8.0 hemoglobin, liver levels, and total bilirubin levels three times the normal level in the laboratory
3. A person who is confirmed to be undergoing renal replacement treatment such as dialysis due to acute or terminal nephropathy during screening
4. A person who has been diagnosed with cancer within 6 months at the time of screening or has been treated for cancer has been confirmed to have recurrent or metastatic cancer.
5. A person who has been confirmed to be taking medication for liver diseases such as liver cirrhosis during screening
6. A person who is pregnant and nursing. However, women of childbearing age can participate only if it is certain that they are not pregnant. Women of childbearing age are defined as women except those who have not clearly undergone menopause or are unable to conceive by surgical procedures.
7. A patient with a history of hemorrhagic tendencies, gastrointestinal hemorrhage
8. Patients who have difficulty explaining and expressing their opinions on participation in the study due to decreased consciousness at the time of acquisition of consent
9. A person who judges that the tester is not appropriate for participation in the clinical trial for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of Apixaban; The intervention group will receive Apixaban 2.5mg or Apixaban 5mg	Drug: Administration of Apixaban; Apixaban 2.5mg BID or Apixaban 5mg BID
Other: Administration of Edoxaban; The control group will receive Edoxaban 15mg or 30mg or 60mg	Drug: Administration of Edoxaban; Edoxaban 15mg QD or Edoxaban 30mg QD or Edoxaban 60mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain MR findings (Differences in the incidence of new brain lesions)	Brain MR findings evaluated at 24 months after the first dose of clinical trial-related drugs (new cerebral infarction (including asymptomatic), white matter hyperintensity, microhemorrhage, etc.)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major cardio-cerebrovascular events	Major cardio-cerebrovascular events that occurred within 12 and 24 months after the first dose of the clinical trial-related drug	12 and 24 months
Modified Rankin scale	Modified Rankin scale evaluated at 12 months and 24 months after the first dose of clinical trial-related drugs. Modified Rankin scale is a total of 7 points scale (0-6). 0 - No symptoms.; - No significant disability. Able to carry out all usual activities, despite some symptoms.; - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; - Moderate disability. Requires some help, but able to walk unassisted.; - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; - Dead.	12 and 24 months
NIHSS (National Institute of Health Stroke Scale)	Changes in NIHSS evaluated at 12 and 24 months after first dose of clinical trial-related drug. NIHSS scale is a total of 43 points scale (0-42) This scale means that the lower the score, the better the prognosis, and the higher the score, the higher the possibility of disability.	12 and 24 months
Other finding of brain MR (Differences in the incidence of new brain lesions)	Other finding of brain MR performed 24 months after the first administration of the clinical trial-related drug (cerebrovascular findings, superficial siderosis, brain volume, etc.)	24 months

Collaborators and Investigators

• Sponsor: Ewha Womans University Seoul Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Apixaban; Edoxaban; Non-Vitamin K Antagonist Oral Anticoagulants
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Stroke; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Apixaban; Edoxaban
• Other Study ID Numbers: SEUMC 2024-08-070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No