Clinical trial NCT02129920: RELAXED: Recurrent Embolism Lessened by Rivaroxaban for Acute Ischemic Stroke
Official title: 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)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Stroke, Acute
Atrial Fibrillation
Keywords: 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
Lead sponsor: Japan Cardiovascular Research Foundation
Sponsor class: OTHER
First posted: 2014-05-02
Enrollment: 2000
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive acute ischemic stroke/TIA patients with nonvalvular atrial fibrillation and treated with rivaroxaban

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Recurrent ischemic stroke and major bleeding
timeFrame: 3 monhths
Secondary outcomes:
measure: ischemic stroke and transient ischemic attack
timeFrame: 3 months
measure: Composite cardiovascular events
timeFrame: 3 months
measure: Any bleeding events
timeFrame: 3 months
measure: Intracranial hemorrhage
timeFrame: 3 months
measure: Hemorrhagic transformation of cerebral infarcts
timeFrame: 3 months
measure: Adverse event
timeFrame: 3 month
measure: Recurrence of ischemic stroke and major bleeding according to whether or not heparin is administered
timeFrame: 3 months
measure: Recurrence of ischemic stroke and major bleeding according to whether rivaroxaban is administered in the morning or evening
timeFrame: 3 month
measure: Duration of hospitalization
timeFrame: 3 month
measure: Safety and efficacy of rivaroxaban administration via tube or by crush tablet
timeFrame: 3 month
measure: Definite clinical data on patients developing recurrent ischemic stroke or intracranial hemorrhage during rivaroxaban medication
timeFrame: 3 month
measure: Medical expenditures using a model
timeFrame: 3 month
Other outcomes:
Locations:
city: Suita
country: Japan
facility: Japan Cardiovascular Research Foundation
state: Osaka
Study officials:
affiliation: Japan Cardiovascular Research Foundation, and National Cerebral and Cardiovascular Center
name: Kazuo Minematsu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koge J, Yamagami H, Toyoda K, Yasaka M, Hirano T, Hamasaki T, Nagao T, Yoshimura S, Fujishige M, Tempaku A, Uchiyama S, Mori E, Koga M, Minematsu K. Early initiation of rivaroxaban after reperfusion therapy for stroke patients with nonvalvular atrial fibrillation. PLoS One. 2022 Apr 6;17(4):e0264760. doi: 10.1371/journal.pone.0264760. eCollection 2022.
citation: Yasaka M, Minematsu K, Toyoda K, Yamagami H, Yoshimura S, Nagao T, Mori E, Hirano T, Hamasaki T, Yamaguchi T. Design and Rationale of the RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) Study. J Stroke Cerebrovasc Dis. 2016 Jun;25(6):1342-8. doi: 10.1016/j.jstrokecerebrovasdis.2016.01.035. Epub 2016 Mar 14.