UMIN-CTR Clinical Trial

Public title

Cilostazol Stroke Prevention Study for Antiplatelet Combination

Acronym

CSPS.com (Cilostazol Stroke Prevention Study. Combination)

Scientific Title

Cilostazol Stroke Prevention Study for Antiplatelet Combination

Scientific Title:Acronym

CSPS.com (Cilostazol Stroke Prevention Study. Combination)

Region

Japan

Condition

Noncardioembolic cerebral infarction

Classification by specialty

Medicine in general	Cardiology	Neurology
Geriatrics	Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To examine the efficacy and safety of dual antiplatelet therapy (DAPT) including cilostazol (Pletaal OD Tablet ®) in comparison with antiplatelet monotherapy (excluding cilostazol) for secondary prevention of ischemic stroke in high-risk patients for stroke

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Recurrence of symptomatic ischemic stroke,with the symptoms lasting for at least 24 hours
(An "ischemic stroke" hereafter indicates a symptomatic ischemic stroke.)

Key secondary outcomes

Efficacy
- Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)]
- SAH or ICH
- IS or transient ischemic attack (TIA)
- Death from any cause
- Stroke (IS,ICH,SAH), myocardial infarction (MI), or vascular death
- All vascular events: stroke, MI, and other vascular events (e.g. aortic dissection or rupture; pulmonary embolism; heart failure, angina pectoris, or occlusive arteriosclerosis requiring hospitalization; revascularization of coronary artery, aorta, peripheral artery, etc.)

Safety
- Adverse events and adverse drug reactions
- Severe or life-threatening hemorrhage (GUSTO Criteria)

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 considered as a block.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Monotherapy group:
Aspirin (81mg or 100mg) or clopidogrel (50mg or 75mg) will be orally administered once daily.
The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.

Interventions/Control_2

DAPT group:
Cilostazol (100mg twice daily) will be orally administered in combination with aspirin (81 or 100mg once daily) or clopidogrel (50 or 75mg once daily).
The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.

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

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Patients with a diagnosis of noncardioembolic IS that developed between 8 and 180 days before the start of the protocol treatment
2) Patients with a responsible lesion identified by MRI
3) Patients aged 20 to 85 years old when providing informed consent
4) Patients taking clopidogrel or aspirin alone as antiplatelet therapy when providing informed consent
5) Patients meeting at least one of the following criteria a-c:
a. at least 50% stenosis of a major intracranial artery (to the level of A2, M2, or P2)
b. at least 50% stenosis of an extracranial artery (the common carotid artery, internal carotid artery, vertebral artery, brachiocephalic artery, or subclavian artery)
c. Two or more of the following risk factors
- Aged 65 years or more
- Diabetes mellitus
- Hypertension
- Peripheral arterial disease
- Chronic kidney disease
- History of IS (excluding the index IS for this study)
- History of ischemic heart disease
- Smoking (only current smokers)
6) Patients considered to be able to visit the study site for ambulatory care throughout the observation period
7) Patients who provided written informed consent

Key exclusion criteria

1) Patients with emboligenic heart disease
2) Patients taking any anticoagulant agents
3) Patients who cannot undergo MRI examination for reasons such as claustrophobia and implanted pacemaker
4) Patients scheduled to undergo any surgery, such as percutaneous angioplasty, stent placement, and bypass grafting, during the study period
5) Patients with a drug-eluting coronary stent implanted within one year
6) Patients with a history of symptomatic non-traumatic intracranial hemorrhage, any other hemorrhagic disease (eg, active peptic ulcer), bleeding predisposition, or blood clotting disorders
7) Patients with a history of hypersensitivity to cilostazol
8) Patients with congestive heart failure or uncontrolled angina pectoris
9) Patients with thrombocytopenia (platelet count <= 100,000/mm3)
10) Patients with severe liver or renal dysfunction
11) Women who are pregnant, breast-feeding, or of child-bearing potential
12) Patients with a malignant tumor requiring treatment
13) Patients who are taking aspirin, and meet any of the following criteria:
- History of hypersensitivity to aspirin or salicylic acid analogues
- Current peptic ulcer
- Aspirin-induced asthma or its history
14) Patients who are taking clopidogrel, and meet the following criterion:
- History of hypersensitivity to clopidogrel
15) Patients who are participating in any other clinical studies
16) Patients considered by the investigator/subinvestigator to be unsuitable for participating in this study

Target sample size

4000

Name of lead principal investigator

1st name
Middle name
Last name	Takenori Yamaguchi

Organization

National Cerebral and Cardiovascular Center

Division name

President emeritus

Zip code

Address

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

TEL

06-6833-5012

Email

tyamaguc@ncvc.go.jp

Name of contact person

1st name
Middle name
Last name	Minoru Ido

Organization

Japan Cardiovascular Research Foundation

Division name

Cilostazol Stroke Prevention Study. Combination secretariat

Zip code

Address

Osaka Kogin Bldg.,4-1-1 Koraibashi,Chuo-ku,Osaka,541-0043,Japan

TEL

0120-05-3125

Homepage URL

http://www.jcvrf.jp/research/shitei_kenkyu.html

Email

prj-csps.cont.com@eps.co.jp

Institute

Otsuka Pharmaceutical Co., Ltd.

Institute

Department

Personal name

Organization

Otsuka Pharmaceutical Co., 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

NCT01995370

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

一宮西病院（愛知県）／Ichinomiyanishi Hospital(Aichi)、釧路労災病院（北海道）／Kushiro Rosai Hospital(Hokkaido)、由利組合総合病院（秋田県）／Yuri Kumiai General Hospital(Akita)／東京女子医科大学病院（東京都）／Tokyo Women's Medical University Hospital(Tokyo)、新渡戸記念中野総合病院（東京都）／Nitobe Memorial Nakano General Hospital(Tokyo)、道東脳神経外科病院（北海道）／Doutou neurosurgery(Hokkaido)、神戸市立医療センター中央市民病院（兵庫県）／Kobe City Medical Center General Hospital(Hyogo)、城山病院（大阪府）／Shiroyama Hospital(Osaka)、宇部興産株式会社中央病院（山口県）／Ube Kohsan Central Hospital(Yamaguchi)、神戸掖済会病院（兵庫県）／Kobe Ekisaikai Hospital(Hyogo)、聖麗メモリアル病院（茨城県）／Seirei Memorial Hospital(Ibaragi)、黒部市民病院（富山県）／Kurobe City Hospital(Toyama)、さくら会病院（大阪府）／Sakurakai Hospital(Osaka)、鹿児島医療センター（鹿児島県）／Kagoshima Medical Center(Kagoshima)、小樽市立病院（北海道）／Otaru General Hospital(Hokkaido)、国立循環器病研究センター（大阪府）／National Cerebral and Cardiovascular Center(Osaka)、佐賀大学医学部付属病院（佐賀県）／Saga University Hospital(Saga)、北里大学メディカルセンター（埼玉県）／Kitasato University Medical Center(Saitama)、柏葉脳神経外科病院（北海道）／Kashiwaba Neurosurgical Hospital(Hokkaido)、伊達赤十字病院（北海道）／Date Red Cross Hospital(Hokkaido)、大同病院（愛知県）／Daido Hospital(Aichi)、市立敦賀病院（福井県）／Municipal Tsuruga Hospital(Fukui)、東邦大学医療センター大森病院（東京都）／Toho University Omori Medical Center(Tokyo)、東京山手メディカルセンター（東京都）／Tokyo Yamate Medical Center(Tokyo)、姫路赤十字病院（兵庫県）／Japanese Red Cross Society Himeji Hospital(Hyogo)、洲本伊月病院（兵庫県）／Sumoto Itsuki Hospital(Hyogo)、聖マリア病院（福岡県）／St.Mary's Hospital(Fukuoka)、仙台医療センター（宮城県）／Sendai Medical Center(Miyagi)、島根大学医学部附属病院（島根県）／Shimane University Hospital(Shimane)、高木病院（福岡県）／Takagi Hospital(Fukuoka)、中村記念病院（北海道）／Nakamura　Memorial Hospital(Hokkaido)、旭川医療センター（北海道）／Asahikawa Meidical Center(Hokkaido)、富山大学附属病院（富山県）／Toyama University Hospital(Toyama)、九州医療センター（福岡県）／Kyushu Medical Center(Fukuoka)、岡山赤十字病院（岡山県）／Japan Red Cross Okayama Hospital(Okayama)、札幌白石記念病院（北海道）／Sapporo Shiroishi Memorial Hospital(Hokkaido)、旭川リハビリテーション病院（北海道）／Asahikawa Rehabilitation Hospital(Hokkaido)、総合南東北病院（福島県）／Southern TOHOKU General Hospital(Fukushima)、東京慈恵会医科大学附属病院（東京都）／Jikei University(Tokyo)、済生会横浜市東部病院（神奈川県）／Saiseikai Yokohamashi Tobu Hospital(Kanagawa)、横浜新都市脳神経外科病院（神奈川県）／Yokohamashintoshi Neurosurgical Hospital(Kanagawa)、兵庫医科大学病院（兵庫県）／Hyogo College of Medicine Hospital(Hyogo)、藤枝平成記念病院（静岡県）／Fujieda Heisei Memorial Hospital(Shizuoka)、旭川赤十字病院（北海道）／Japanese Red Cross Asahikawa Hospital(Hokkaido)、製鉄記念八幡病院（福岡県）／Steel Memorial Yawata Hospital(Fukuoka)、川崎医科大学総合医療センター（岡山県）／Kawasaki Medical School General Medical Center(Okayama)、大川原脳神経外科病院（北海道）／Ohkawara Neurosurgical Hospital(Hokkaido)、留萌セントラルクリニック（北海道）／Rumoecentoral clinic(Hokkaido)、岩手医科大学付属病院（岩手県）／Iwate Medical University (Iwate)、福島赤十字病院（福島県）／Japanese Red Cross　Fukushima Hospital(Fukushima)、東京医療センター（東京都）／Tokyo Medical Center(Tokyo)、順天堂大学医学部附属順天堂医院（東京都）／Juntendo University Hospital(Tokyo)、順天堂大学医学部附属静岡病院（静岡県）／Juntendo University Shizuoka Hospital(Shizuoka）、安城更生病院（愛知県）／Anjo Kosei Hospital(Aichi)、トヨタ記念病院（愛知県）／TOYOTA Memorial Hospital(Aichi)、豊田厚生病院（愛知県）／Toyota Kosei Hospital(Aichi)、市立四日市病院（三重県）／Yokkaichi Municipal Hospital(Mie)、美原記念病院（群馬県）／Mihara Memorial Hospital(Gunma)、他231施設

Date of disclosure of the study information

2013

Year

10

Month

31

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://www.webmd.com/stroke/news/20190207/drug-may-be-safer-option-against-repeat-stroke#1

Number of participants that the trial has enrolled

1884

Results

The study found the risk of another ischemic stroke was halved for patients who took Pletal plus aspirin or clopidogrel, versus those who took aspirin or clopidogrel alone.
Specially, 29 of 913 patients (3.2 percent) who took Pletal plus another blood thinner went on to have another stroke, compared to 64 of 926 patients (6.9 percent) who took aspirin or clopidogrel alone, the investigators found.

Results date posted

2019

Year

03

Month

25

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2019

Year

03

Month

06

Day

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2013

Year

09

Month

15

Day

Date of IRB

2013

Year

09

Month

27

Day

Anticipated trial start date

2013

Year

11

Month

10

Day

Last follow-up date

2018

Year

03

Month

31

Day

Date of closure to data entry

2018

Year

12

Month

07

Day

Date trial data considered complete

2018

Year

12

Month

07

Day

Date analysis concluded

Other related information

Registered date

2013

Year

10

Month

31

Day

Last modified on

2019

Year

03

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014239