title: 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.
abstract: BACKGROUND
  In the acute phase of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF), the recurrence rate is high. Nonvitamin K antagonist oral anticoagulants may be appropriate for prevention of early recurrence because they have a much lower risk of hemorrhagic stroke than warfarin.
  
  
  METHODS
  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 is an observational study designed to investigate the optimal timing to start administration of rivaroxaban for prevention of recurrence in NVAF patients in the acute phase of cardioembolic stroke (ClinicalTrials.gov: NCT02129920 and UMIN-clinical trials registry: UMIN000013932). It will evaluate the efficacy and safety of rivaroxaban with regard to infarct size, timing of initiation of rivaroxaban medication, and other patient characteristics. A total of 2000 consecutive patients with acute ischemic stroke in the territory of the middle cerebral artery and NVAF will be enrolled in 100 institutes throughout Japan, and they will receive rivaroxaban within 30 days of the index stroke for secondary prevention of stroke. The infarct size within 48 hours after stroke onset will be measured by diffusion-weighted magnetic resonance imaging. The primary efficacy endpoint is recurrent ischemic stroke, and the primary safety endpoint is major bleeding during the observational period of 3 months after stroke onset. The optimal timing to start treatment with rivaroxaban during the acute stage of ischemic stroke will be determined by analysis of the correlation between primary endpoints and the size of cerebral infarct.
  
  
  CONCLUSIONS
  The RELAXED observational registry study will elucidate the optimal timing of the initiation of rivaroxaban in acute cardioembolic stroke associated with NVAF.
authors.affiliation: Department of Cerebrovascular Medicine and Neurology, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan. Electronic address: yasaka@kyumed.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yasaka
authors.affiliation: Japan Cardiovascular Research Foundation, Suita, Japan; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toyoda
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamagami
authors.affiliation: Department of Neurosurgery, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Neurology, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nagao
authors.affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate, School of Medicine, Sendai, Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
authors.affiliation: Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Advanced Medical Technology Development, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Japan Cardiovascular Research Foundation, Suita, Japan; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D020766:Intracranial Embolism / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D007564:Japan; D012008:Recurrence; D012042:Registries; D012107:Research Design; D012307:Risk Factors; D000069552:Rivaroxaban / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
keywords: Nonvalvular atrial fibrillation; design; rivaroxaban; secondary prevention