UMIN-CTR Clinical Trial

Public 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)

Acronym

RELAXED: Recurrent Embolism Lessened by Rivaroxaban for Acute Ischemic Stroke

Scientific 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)

Scientific Title:Acronym

RELAXED: Recurrent Embolism Lessened by Rivaroxaban for Acute Ischemic Stroke

Region

Japan

Condition

Stroke, Acute TIA
Non-valvular Atrial Fibrillation

Classification by specialty

Cardiology	Neurology	Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective of the study is to evaluate the efficacy and safety of an oral direct activated coagulation factor Xa inhibitor, rivaroxaban, for acute ischemic stroke patients with non-valvular atrial fibrillation 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.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

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)

Key secondary outcomes

1) ischemic stroke and transient ischemic attack
2) 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) Any bleeding events
4) Intracranial hemorrhage
5) Hemorrhagic transformation of cerebral infarcts
6) Adverse event
7) Recurrence of ischemic stroke and major bleeding according to whether or not heparin is administered
8) Recurrence of ischemic stroke and major bleeding according to whether rivaroxaban is administered in the morning or evening
9) Duration of hospitalization
10) Safety and efficacy of rivaroxaban administration via tube or by crush tablet
11) Definite clinical data on patients developing recurrent ischemic stroke or intracranial hemorrhage during rivaroxaban medication
12) Medical expenditures using a model

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Clinical diagnosis of acute ischemic stroke or transient ischemic attack (TIA)
2) Having non-valvular atrial fibrillation
3) 20 years or older
4) Visiting the clinic/hospital within 48 hours of the onset of acute ischemic stroke or TIA
5) Identification of an infarct in the middle cerebral artery (MCA) territory (symptoms ascribable to ischemia in the MCA territory in TIA patients)
6) Initiation of treatment with rivaroxaban within 30 days of the onset of acute ischemic stroke or TIA
7) Written informed consent by patients or their legally acceptable representative

Key exclusion criteria

1) hypersensitivity to rivaroxaban
2) Active bleeding (clinically significant hemorrhage) including gastrointestinal hemorrhage
3) liver disease complicated with coagulation disorder
4) liver disorder corresponding to Child-Pugh Class B or C
5) renal failure (creatinine clearance: <15 mL/minute)
6) poorly controlled hypertension (higher than 180/100)
7) Woman who are or are likely to be pregnant
8) Ongoing treatment with HIV protease inhibitors including ritonavir, atazanavir and indinavir
9) Ongoing treatment with itraconazole, voriconazole and ketoconazole
10) Active bacterial endocarditis
11) Patients considered by the investigator to be unsuitable for participating in this study

Target sample size

2000

Name of lead principal investigator

1st name
Middle name
Last name	Kazuo Minematsu, M.D.

Organization

National Cerebral and Cardiovascular Center
Japan Cardiovascular Research Foundation

Division name

Deputy Director General of the Hospital

Zip code

Address

5-7-1 Fujishiro-dai, Suita, Osaka, Japan

TEL

06-6833-5012

Email

kminemat@ncvc.go.jp

Name of contact person

1st name
Middle name
Last name	Satoko Matsumoto

Organization

Japan Cardiovascular Research Foundation, and National Cerebral and Cardiovascular Center

Division name

Secretariat

Zip code

Address

5-7-1 Fujishiro-dai, Suita, Osaka, Japan

TEL

06-6872-0010

Homepage URL

http://portal.e-trial.co.jp/relaxed/

Email

relaxed@jcvrf.jp

Institute

Japan Cardiovascular Research Foundation, and National Cerebral and Cardiovascular Center

Institute

Department

Personal name

Organization

Bayer Yakuhin, Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT02129920

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立循環器病研究センター（大阪府）、東京女子医科大学病院（東京都）、国立病院機構九州医療センター（福岡県）、国立病院機構名古屋医療センター（愛知県）、川崎医科大学附属病院（岡山県）、埼玉医科大学国際医療センター（埼玉県）、岩手医科大学附属病院（岩手県）、熊本市民病院（熊本県）、聖マリアンナ医科大学病院（神奈川県）、北海道大学病院（北海道）、広島大学病院（広島県）、兵庫医科大学病院（兵庫県）、他、約100施設

National Cerebral and Cardiovascular Center (Osaka), Tokyo Women’s Medical University Hospital (Tokyo), NHO Kyushu Medical Center (Fukuoka), NHO Nagoya Medical Center (Aichi),Kawasaki Medical School Hospital (Okayama), Saitama Medical University International Medical Center(Saitama), Iwate Medical University Hospital (Iwate)， Kumamoto City Hospital(Kumamoto),St Marianna University School of Medicine Hospital (Kanagawa),Hokkaido University Hospital (Hokkaido), Hiroshima University Hospital (Hiroshima), The Hospital of Hyogo College of Medicine(Hyogo), and 100 medical institutes approximately

Date of disclosure of the study information

2014

Year

05

Month

12

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2013

Year

12

Month

12

Day

Date of IRB

Anticipated trial start date

2014

Year

02

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

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.

Registered date

2014

Year

05

Month

12

Day

Last modified on

2014

Year

05

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016247