UMIN-CTR Clinical Trial

Public title

AFIRE Study: Atrial Fibrillation and Ischemic events with Rivaroxaban in patiEnts with stable coronary artery disease Study

Acronym

AFIRE Study

Scientific Title

AFIRE Study: Atrial Fibrillation and Ischemic events with Rivaroxaban in patiEnts with stable coronary artery disease Study

Scientific Title:Acronym

AFIRE Study

Region

Japan

Condition

Non-valvular atrial fibrillation

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the efficacy and safety of rivaroxaban monotherapy compared to rivaroxaban in co-administration with a single anti-platelet therapy in non-valvular atrial fibrillation patients with stable coronary artery diseases.
For the efficasy of rivaroxaban monotherapy, for the composite endpoint incidence of cardiovascular events or all-cause mortality for the rivaroxaban and anti-platelet drugs single agent combination therapy to verify the non-inferiority. for safety, to verify the superiority for serious bleeding complications incidence.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

(1)Primary efficacy endpoints
Composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularizations or all-cause mortality)
(2)Safety primary endpoints
Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH)

Key secondary outcomes

1)Net adverse clinical and cerebral events (NACCE) (net clinical benefit)
All-cause death, myocardial infarction, stroke and major bleeding
2)Ischemic cardiovascular events and death
(1)All-cause mortality
(2)Cardiovascular death
(3)Non-cardiovascular death
(4)Myocardial infarction
(5)Unstable angina pectoris requiring revascularization
(6)Ischemic stroke
(7)Transient ischemic attack
(8)Systemic embolism
(9)PCI/CABG
(10)Stent thrombosis
(11)Ischemic stroke and systemic embolism
3)Any bleeding
4)Adverse events excluding hemorrhagic events
5)Comparison of the primary endpoints between patients treated with aspirin and treated with thienopyridine derivatives
6)Stratified analysis of the primary endpoints, ischemic cardiovascular events and mortality according to the CHADS2 score and CHA2DS2-VASc score
7)Stratified analysis of the incidences of the primary endpoints, ischemic cardiovascular events and mortality according to subject characteristics
8)Stratified analysis of major bleeding and all bleeding events in patients treated concomitantly with any antiplatelet and patients not treated with any antiplatelet according to the HAS-BLED score and analysis of specificity and sensitivity
9)Comparison of the incidence of bleeding events according to whether or not proton pump inhibitors (PPIs) are used
10)Comparison of the incidences of the primary endpoints according to whether rivaroxaban is administered in the morning or evening
11)Investigation of relationships between ischemic cardiovascular events, bleeding events/adverse events and discontinuation of treatment with antithrombotic agents
12)Investigation of relationships between prothrombin time at trough and bleeding events and the cutoff values according to whether or not antiplatelet drugs are concomitantly used
13)The incidence of the primary endpoints according to adherence

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

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

Rivaroxaban monotherapy
Rivaroxaban will be orally administered at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min until end of study.

Interventions/Control_2

Rivaroxaban co-administered with single anti-platelet therapy
Rivaroxaban and a single antiplatelet will be orally administered until end of study. Antiplatelet will be selected from aspirin or thienopyridine derivatives (clopidogrel or prasugrel).
Rivaroxaban administration: Rivaroxaban will be orally administered after a meal at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min (regardless of time).
Aspirin administration: Aspirin will be orally administered once a day at a dose of 81 mg or 100 mg.
Clopidogrel administration: Clopidogrel will be orally administered once a day after a meal at a dose of 75 mg. The dose will be reduced to 50mg once a day by consideration for aging, body weight or clinical findings.
Prasugrel administration: Prasugrel will be orally administered once a day at a dose of 3.75 mg. If the body weight is 50kg or less than 50kg, the dose will be considered to reduce to 2.5 mg once a daily by evaluation for aging, renal function or other bleeding risk and thrombotic risk.

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

Patients with non-valvular atrial fibrillation complicated with stable coronary artery disease who are 20 years or more at the obtaining of informed consent, CHADS2 score are 1 or more, and fulfil the criteria below and can provide written consent for participation in the present study will be eligible.
1) Patients who underwent percutaneous coronary intervention, including plain old balloon angioplasty, at least one year ago
2) Patients who have coronary stenosis requiring no percutaneous coronary intervention (50% or more stenosis) as indicated by coronary CT or coronary angiography
3) Patients who underwent coronary artery bypass graft CABG at least one year ago

Key exclusion criteria

1)Patients who are contraindicated for rivaroxaban
2)Patients who are contraindicated for aspirin, thienopyridine derivatives (clopidogrel or prasugrel)
3)Patients who underwent PCI, including POBA, in the past one year
4)Patients who are going to undergo revascularization
5)Patients who have a past history of stent thrombosis
6)Those who are going to undergo invasive surgery (excluding digestive endoscopy and biopsy)
7)Patients who have active tumors
8)Patients who have poorly-controlled hypertension (systolic blood pressure at hospital admission based on two or more measurements: 160 mmHg or more)
9)Patients who cannot discontinue treatment with antiplatelet drugs (the physician in charge will make a decision on the basis of the lesion shape, lesion site and type of stents.)
(10)Patients judged as inappropriate for this study by investigators

Contraindicated for rivaroxaban
(1)Unstable CAD
(2)Patients with a past history of stent thrombosis
(3)Patients judged as inappropriate for this study by investigators

Target sample size

2200

Name of lead principal investigator

1st name
Middle name
Last name	Satoshi yasuda

Organization

Japan Cardiovascular Research Foundaition

Division name

National Cerebral and Cardiovascular Center

Zip code

Address

5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

TEL

+81-6-6872-0010

Email

afire@jcvrf.jp

Name of contact person

1st name
Middle name
Last name	Saburo Saito

Organization

Japan Cardiovascular Research Foundation

Division name

Administration Office

Zip code

Address

5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan

TEL

06-6872-0010

Homepage URL

Email

afire@jcvrf.jp

Institute

Japan Cardiovascular Research Foundation

Institute

Department

Personal name

Organization

Bayer Yakuhin , Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

独立行政法人 国立循環器病研究センター（大阪府）
熊本大学医学部附属病院（熊本県）
大阪医科大学（大阪府）

Date of disclosure of the study information

2015

Year

02

Month

23

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

Terminated

Date of protocol fixation

2014

Year

12

Month

26

Day

Date of IRB

2014

Year

12

Month

19

Day

Anticipated trial start date

2015

Year

01

Month

01

Day

Last follow-up date

2018

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

02

Month

23

Day

Last modified on

2019

Year

03

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019280