Clinical trial NCT05089435: An Open-label Study of EZYPRO® in Atrial Fibrillation Detection on ESUS Patients
Official title: An Open-label Study to Evaluate the Effectiveness and Safety of EZYPRO® in Atrial Fibrillation Detection in Nearly Embolic Stroke of Undetermined Source (ESUS) Patient
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atrial Fibrillation
Embolic Stroke of Undetermined Source
Keywords: ESUS, stoke, arrhythmia, atrial fibrillation, ECG patch, continuous ECG monitoring
Lead sponsor: Sigknow Biomedical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-22
Enrollment: 500
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients should wear simultaneously the trial device EZYPRO and a 24-hr Holter monitor.
Primary purpose: DIAGNOSTIC

Brief summary: The aim of the study is to evaluate the effectiveness and safety of the 14-day continuous ECG patch monitor (EZYPRO®) compared with a 24-hour Holter monitor in the detection of atrial fibrillation (AF) among ESUS patients.


Eligibility criteria: Inclusion Criteria:

1. Patients are male or female, aged ≥ 50 years.
2. Patients must be able to understand and sign the informed consent documents within 10 days of ischemic stroke diagnosis and aware of the investigational nature of the study.
3. Patients must be willing to comply with protocol stated requirements, instructions, and restrictions during the study.
4. Patients who have stable vital signs for at least 24 hours, defined as normal respiration, afebrile, and systolic blood pressure ≤ 220 mmHg.
5. Patients who are diagnosed with acute ischemic stroke and undergo a diagnostic workup using brain magnetic resonance imaging (MRI), brain magnetic resonance angiography (MRA), 12-lead ECG, carotid duplex ultrasound, with or without transcranial color-coded duplex sonography (TCCS), and cardiac echo (transthoracic echocardiography \[TTE\]) to meet the concept of "nearly embolic stroke of undetermined source (ESUS)" as defined by the following criteria:

   a. Acute cerebral infarct, as identified by hyperintensity in diffusion-weighted imaging (DWI) of MRI and hypointensity for apparent diffusion coefficient (ADC) b. DWI of MRI showing non-lacunar stroke, defined as a subcortical infarct ≤ 2.0 cm in largest dimension within the territory of the small penetrating cerebral arteries c. Absence of ≥ 50% stenosis of the intracranial or extracranial artery associated with the infarcted lesion as confirmed by brain MRA, carotid duplex, and/or TCCS d. No medical history of AF e. No major-risk cardioembolic sources including AF, atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, recent (\< 4 weeks) myocardial infarction, left ventricular ejection fraction \< 30%, valvular vegetations or infective endocarditis f. No other specific cause of stroke identified (e.g., arteritis, dissection, migraine, and cancer-related hypercoagulability etc.) g. Not ischemic stroke located at specific regions or severe hemorrhagic infarct identified by brain MRI, including: (i.) Large pontine infarct, which more likely belongs to branch artery disease (BAD) (ii.) Anterior choroidal artery infarct (iii.) Internal border zone infarct, represented with rosary-like pattern of lesions between the territories of lenticulostriate artery and superficial branch of middle cerebral artery (MCA) (iv.) Severe hemorrhagic transformation of acute ischemic stroke, which may impede the usage of antiplatelet agents or anticoagulant within 14 days post-stroke per the investigator's judgment

Exclusion Criteria:

1. Patients with the following skin related issues that could put patients at risk, interfere with study evaluations, or prevent meeting the requirements of the study:

   1. Intolerable, severe skin allergies to the 24-hour Holter monitor or 14-day EZYPRO® or history of severe skin allergies to medical adhesive bandages
   2. Any injury, eczema, dermatitis, chromatosis, or abnormality at the skin site where devices are applied
   3. Hyperhidrosis
2. Patients who have contraindication to either of the antiplatelet agents which might be used in this study (i.e. aspirin and/or clopidogrel) or to all types of non-vitamin K antagonist oral anticoagulant (NOAC) (due to allergy, mechanical valve replacement, renal insufficient with creatinine clearance \[CCr\] \< 15 ml/min, moderate to severe mitral stenosis, etc.).
3. Patients who are evaluated as Modified Rankin Scale \> 4.
4. Mental/physical/social condition (including dementia) which could preclude performing efficacy or safety assessments.
5. Patients with following condition or diseases:

   1. Medical history of major bleeding impeding usage of antiplatelet agents or NOAC
   2. Medical history of brain or other clinically significant neurological/cardiovascular disorders or injuries other than ischemic stroke in the opinion of the investigator
   3. Clinically significant or unstable gastrointestinal, renal, hepatic, endocrine, pulmonary, or cardiovascular disease, including not well controlled hypertension, chronic obstructive pulmonary disease, and diabetes that would hinder or interfere participation to the study in the opinion of the investigator
6. Patients who need to receive anticoagulation therapy prior to the screening visit.
7. Patients who meet following conditions:

   1. Patients who are scheduled to receive surgery that may have to stop anticoagulation or antiplatelet therapy during the study period
   2. Patients who are scheduled to receive neurological or cardiovascular intervention during the trial period
8. Patients who are unable to undergo brain MRI for any reason.
9. Currently participating in another trial or who participated in a previous clinical trial and received any treatment which may interfere the study data within 2 weeks prior to the screening visit.
10. Patients who need to receive long-term (\> 21 days) dual antiplatelet therapy or anticoagulant therapy prior to AF detection after study enrollment.

Primary outcomes:
measure: Afib detected by 24-hour Holter
timeFrame: 24 hours
measure: Afib detected by 14-day EZYPRO
timeFrame: 14 days
Secondary outcomes:
measure: Skin irritation by EZYPRO patch
timeFrame: 180 days
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Shin Kong Wu Ho-Su Memorial Hospital
name: Li Ming Lien, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital Hsin-Chu Branch
name: Li Kai Tsai, PhD
role: STUDY_DIRECTOR
References: