RELAXED: Recurrent Embolism Lessened by Rivaroxaban for Acute Ischemic Stroke

Study Overview
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Brief Summary
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Early recurrence of cardioembolic stroke in patients with atrial fibrillation is common, reaching approximately 6% within 30 days after initial stroke. Therefore, it is preferable to provide early anticoagulation for cardioembolic stroke. However, early anticoagulation may increase the risk of hemorrhagic transformation of cerebral infarcts. It is difficult to decide the timing of initiation for anticoagulant therapy in stroke patients with non-valvular atrial fibrillation (NVAF). In 2013 the European Heart Rhythm Association presented the practical guides for oral anticoagulants in NVAF patients, which recommend that the optimal time to start anticoagulant therapy should be determined according to the stroke severity. However, this recommendation is principally an experts' opinion and is not suitable in the clinical practice in Japan. RELAXED, a multicenter observational study is planned to evaluate the efficacy and safety of an oral direct activated coagulation factor Xa inhibitor, rivaroxaban, for acute ischemic stroke patients with NVAF in consideration of the infarct size, timing of initiation for rivaroxaban medication, and other patient characteristics, and thereby to determine the optimal timing of the initiation during acute ischemic stroke. The consecutive acute ischemic stroke / transient ischemic attack (TIA) patients with NVAF who are treated with rivaroxaban will be enrolled. The infarction size at 0-48 hours after stroke onset will be measured by the diffusion weighted image (DWI) MRI. The primary efficacy endpoint is recurrent ischemic stroke within 3 months. The primary safety endpoint is major bleedings within 3 months. The optimal timing to initiate rivaroxaban during acute ischemic stroke is determined by analysis of co-relation between primary endpoints and the infarct size / time to initiate rivaroxaban.

Official Title
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Recurrent Embolism Lessened by Rivaroxaban, an Anti-Xa Agent of Early Dosing for Acute Ischemic Stroke and Transient Ischemic Attack With Atrial Fibrillation Study (RELAXED)

Conditions
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Stroke, Acute, Atrial Fibrillation

Intervention / Treatment
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* Other: This is an observational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of acute ischemic stroke or transient ischemic attack (TIA) Having non-valvular atrial fibrillation Visiting the clinic/hospital within 48 hours of the onset of acute ischemic stroke or TIA Identification of an infarct in the middle cerebral artery (MCA) territory (symptoms ascribable to ischemia in the MCA territory in TIA patients) Initiation of treatment with rivaroxaban within 30 days of the onset of acute ischemic stroke or TIA Written informed consent by patients Exclusion Criteria: hypersensitivity to rivaroxaban 2) Active bleeding (clinically significant hemorrhage) including gastrointestinal hemorrhage liver disease complicated with coagulation disorder liver disorder corresponding to Child-Pugh Class B or C renal failure (creatinine clearance: <15 mL/minute) poorly controlled hypertension (higher than 180/100) Woman who are or are likely to be pregnant Ongoing treatment with HIV protease inhibitors including ritonavir, atazanavir and indinavir Ongoing treatment with itraconazole, voriconazole and ketoconazole Active bacterial endocarditis Patients considered by the investigator to be unsuitable for participating in this study

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NVAF, acute ischemic stroke/TIA<br>Consecutive acute ischemic stroke/TIA patients with nonvalvular atrial fibrillation and treated with rivaroxaban | Other: This is an observational study<br> <br> * Other names: This is an observational, not intervention, study.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent ischemic stroke and major bleeding | The optimal timing to start treatment with rivaroxaban of the initiation for during acute ischemic stroke are determined by analysis of co-relation between primary endpoints including recurrent ischemic stroke / major bleeding, and the cerebral infarction size / time to start treatment with rivaroxaban. Major bleeding according to the criteria by the International Society of Thrombosis and Haemostasis (ISTH) | 3 monhths | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ischemic stroke and transient ischemic attack |  | 3 months | 
| Composite cardiovascular events | The composite cardiovascular events are included ischemic stroke, TIA, systemic embolism, acute coronary syndrome, deep vein thrombosis, pulmonary embolism, other ischemic disease, revascularization, total death, cardiovascular death | 3 months | 
| Any bleeding events |  | 3 months | 
| Intracranial hemorrhage |  | 3 months | 
| Hemorrhagic transformation of cerebral infarcts |  | 3 months | 
| Adverse event |  | 3 month | 
| Recurrence of ischemic stroke and major bleeding according to whether or not heparin is administered |  | 3 months | 
| Recurrence of ischemic stroke and major bleeding according to whether rivaroxaban is administered in the morning or evening |  | 3 month | 
| Duration of hospitalization |  | 3 month | 
| Safety and efficacy of rivaroxaban administration via tube or by crush tablet |  | 3 month | 
| Definite clinical data on patients developing recurrent ischemic stroke or intracranial hemorrhage during rivaroxaban medication |  | 3 month | 
| Medical expenditures using a model |  | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Cerebral Infarction, Atrial Fibrillation, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Brain Infarction, Brain Ischemia, Anticoagulants, Hematologic Agents, Therapeutic Uses