UMIN-CTR Clinical Trial

Public title

Optimal Antithrombotic Therapy in Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation and Atherothrombosis

Acronym

ATIS-NVAF study

Scientific Title

Optimal Antithrombotic Therapy in Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation and Atherothrombosis

Scientific Title:Acronym

ATIS-NVAF study

Region

Japan

Condition

Ischemic Stroke
Atrial Fibrillation
Atherothrombosis

Classification by specialty

Medicine in general	Cardiology	Neurology
Geriatrics	Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The Purpose of the study is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Composite endpoint of ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization) and major bleeding defined by the International Society on Thrombosis and Haemostasis(ISTH) criteria within 2 years after randomization

Key secondary outcomes

Incidences of following events within 2years after randomization:

* All-cause mortality
* Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)
* All ischemic cardiovascular events including transient ischemia (cardiovascular death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina pectoris, systemic embolism, progression of symptomatic peripheral artery disease, ischemic events requiring urgent revascularization)
* Ischemic stroke
* Myocardial infarction and cardiovascular death
* ISTH major bleeding
* ISTH major bleeding and clinically relevant non-major bleeding
* Intracranial hemorrhage

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Dual-therapy group: single anticoagulant drug (warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban) and single antiplatelet drug (aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol)

The dosage is determined according to each drug's package insert in Japan.

In patients treated with warfarin, the target INR range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years is recommended according to the Japanese guidelines.

Interventions/Control_2

Single-therapy group: single anticoagulant drug (warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban)

The dosage is determined according to each drug's package insert in Japan.

In patients treated with warfarin, the target INR range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years is recommended according to the Japanese guidelines.

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. Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms
2. Age: 20 years or more.
3. Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant
4. Patients who have one of the following atherothrombotic diseases
a) A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention(PCI)
b) A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting)
c) Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA))
d) Intracranial artery stenosis (=>50% stenosis of the diameter of a major intracranial artery: intracranial internal carotid artery, anterior cerebral artery (ACA)-A1 and A2, middle cerebral artery (MCA)-M1 and M2, posterior cerebral artery (PCA)-P1 and P2, vertebral artery, and basilar artery; a history of intracranial stent placement or intracranial bypass surgery)
e) A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease
5. Patients without severe disability (modified Rankin Scale score =<4)
6. Patients who can take oral medications
7. Patients who can receive follow-up survey
8. Provision of written informed consent either directly or by a suitable surrogate

Key exclusion criteria

1. Patients with a history of myocardial infarction or acute coronary syndrome within the past 12 months
2. Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months
3. Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months
4. History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months
5. Hemorrhagic diathesis or blood coagulation disorders
6. Platelet counts <100,000 /mm3 at enrollment.
7. Severe anemia (hemoglobin <7 g/dL)
8. Severe renal failure (creatinine clearance =<15 mL/min) or who are undergoing chronic hemodialysis.
9. Severe liver dysfunction (Grade B or C of the Child-Pugh classification)
10. Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5)
11. Pregnant or possibly pregnant women
12. Active cancer
13. Expectation of survival less than 2 years
14. Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period
15. Planned revascularization procedure during the follow-up period
16. Patients who are enrolled in other trials
17. Patients judged as inappropriate for this study by investigators

Target sample size

400

Name of lead principal investigator

1st name	Hiroshi
Middle name
Last name	YAMAGAMI

Organization

National Hospital Organization Osaka National Hospital

Division name

Department of Stroke Neurology

Zip code

540-0006

Address

2-1-14 Hoenzaka, Chuo-Ku, Osaka 540-0006 Japan

TEL

+81-6-6942-1331

Email

yamagami-brain@umin.ac.jp

Name of contact person

1st name	Hiroshi
Middle name
Last name	YAMAGAMI

Organization

National Hospital Organization Osaka National Hospital

Division name

Department of Stroke Neurology

Zip code

540-0006

Address

2-1-14 Hoenzaka, Chuo-Ku, Osaka 540-0006 Japan

TEL

+81-6-6942-1331

Homepage URL

https://www.atis-nvaf.net

Email

yamagami-brain@umin.ac.jp

Institute

National Hospital Organization Osaka National Hospital

Institute

Department

Personal name

Organization

The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program (JRISTA)

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Network for Clinical Stroke Trials (NeCST)

Name of secondary funder(s)

Organization

National Hospital Organization Review Board for Clinical Trials (Nagoya)

Address

4-1-1 San-nomaru, Naka-ku, Nagoya, 460-0001, Japan

Tel

052-951-1111

Email

311-nmc-rec@mail.hosp.go.jp

Secondary IDs

YES

Study ID_1

jRCTs051180202

Org. issuing International ID_1

Japan Registry of Clinical Trial

Study ID_2

NCT03062319

Org. issuing International ID_2

ClinicalTrials.gov

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

02

Month

01

Day

URL releasing protocol

https://www.atis-nvaf.net/

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

No longer recruiting

Date of protocol fixation

2016

Year

11

Month

25

Day

Date of IRB

2019

Year

04

Month

23

Day

Anticipated trial start date

2017

Year

05

Month

01

Day

Last follow-up date

2024

Year

04

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

12

Month

23

Day

Last modified on

2022

Year

06

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029222