PreventIon of CArdiovascular Events in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage
NCT ID: NCT01013532
Last Updated: 2015-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE4
1600 participants
INTERVENTIONAL
2009-06-30
2016-12-31
Brief Summary
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The primary hypothesis of this study is; Cilostazol alone or with probucol will reduce the risk of cerebral hemorrhage without increase of cardiovascular events compared to aspirin in the ischemic stroke patients with symptomatic or asymptomatic old cerebral hemorrhage.
This study will prove the superiority of cilostazol on the prevention of cerebral hemorrhagic events without increasing the cardiovascular events against aspirin and the superiority of probucol on the prevention of overall cardiovascular events.
Detailed Description
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Consequently, for the reasons described above, hemorrhagic side effects including cerebral hemorrhage have been a great concern, in the usage of antiplatelet agent or anticoagulant for the secondary prevention in the patients with cerebral infarction.
It is reported that the occurrence of cerebral hemorrhage tends to increase in cases of accompanying lacunar infarction which occurs more frequently in Asians than in Westerners, or periventricular ischemic change which increasingly occurs with ageing. Accordingly, the point is that the occurrence of cerebral hemorrhage should be primarily considered in the treatment of cerebral infarction, along with the phenomenon of an ageing population both in Asian countries including Korea.
Nevertheless, so far there has been no clinical research regarding secondary prevention of stroke, particularly considering the risk of occurrence of hemorrhage in cerebral infarction cases. However, according to a recent study, when phosphodiesterase inhibitors including Cilostazol are used independently, or in combination with aspirin, secondary prevention can be improved without increasing the occurrence of hemorrhagic side effects.
Considering this, if it is proved that the agent, Cilostazol, could decrease the risk of occurrence of stoke, along with no significant increase in the risk of occurrence of hemorrhagic side effects, by selecting a patent group with a high risk of cerebral hemorrhage, the agent (Cilostazol) may be recognized as an unique antiplatelet agent applicable to old-aged patient with cerebral infarction who have a certain risk of cerebral hemorrhage.
* High risk of cerebral hemorrhage is defined as presence of history of cerebral hemorrhage with appropriate neuroimage findings or presence of asymptomatic old cerebral hemorrhage findings(equal or more than 8mm) or multiple microbleeds on the GRE images.
* 1600 ischemic stroke patients with high risk of cerebral hemorrhage will be recruited and they are randomized into four groups (cilostazol plus probucol, aspirin plus probucol, cilostazol and aspirin) by 2X2 factorial design.
* IMT and ABI will be measured every year during follow-up period and the results will be compared with the baseline data. The change of IMT and ABI will be analyzed with the occurrence of cardiovascular events.
* The study will finish at least 1 year after the recruit of 1600th patients. Until the finish, all patients will continuously take study medications and visit every 3months at the study site.
* Brain MRI including FLAIR and GRE will be done at the final visits.
Conditions
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Keywords
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Study Design
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RANDOMIZED
FACTORIAL
PREVENTION
QUADRUPLE
Study Groups
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Cilostazol+ Probucol
100mg cilostazol bid plus probucol plus placebo of aspirin
Cilostazol
Cilostazol 100mg bid
Probucol
Probucol 250mg bid
placebo of aspirin
same size and shape of active aspirin 100mg
ankle-brachial index (ABI)
measurement of ABI every years during follow up
intima-medial thickness (IMT)
ultrasound measured IMT of both common carotid arteries
new asymptomatic brain hemorrhage
asymptomatic macrobleedings or microbleedings on GRE images
new ischemic lesions on follow-up FLAIR images
any new ischemic lesions
Aspirin + Probucol
aspirin plus placebo cilostazol plus probucol
Probucol
Probucol 250mg bid
Aspirin
Aspirin 100mg qd
placebo of cilostazol
same shape and size of active cilostazol
ankle-brachial index (ABI)
measurement of ABI every years during follow up
intima-medial thickness (IMT)
ultrasound measured IMT of both common carotid arteries
new asymptomatic brain hemorrhage
asymptomatic macrobleedings or microbleedings on GRE images
new ischemic lesions on follow-up FLAIR images
any new ischemic lesions
Cilostazol
cilostazol plus placebo of aspirin
Cilostazol
Cilostazol 100mg bid
placebo of aspirin
same size and shape of active aspirin 100mg
ankle-brachial index (ABI)
measurement of ABI every years during follow up
intima-medial thickness (IMT)
ultrasound measured IMT of both common carotid arteries
new asymptomatic brain hemorrhage
asymptomatic macrobleedings or microbleedings on GRE images
new ischemic lesions on follow-up FLAIR images
any new ischemic lesions
Aspirin
aspirin plus placebo of cilostazol
Aspirin
Aspirin 100mg qd
placebo of cilostazol
same shape and size of active cilostazol
ankle-brachial index (ABI)
measurement of ABI every years during follow up
intima-medial thickness (IMT)
ultrasound measured IMT of both common carotid arteries
new asymptomatic brain hemorrhage
asymptomatic macrobleedings or microbleedings on GRE images
new ischemic lesions on follow-up FLAIR images
any new ischemic lesions
Interventions
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Cilostazol
Cilostazol 100mg bid
Probucol
Probucol 250mg bid
Aspirin
Aspirin 100mg qd
placebo of cilostazol
same shape and size of active cilostazol
placebo of aspirin
same size and shape of active aspirin 100mg
ankle-brachial index (ABI)
measurement of ABI every years during follow up
intima-medial thickness (IMT)
ultrasound measured IMT of both common carotid arteries
new asymptomatic brain hemorrhage
asymptomatic macrobleedings or microbleedings on GRE images
new ischemic lesions on follow-up FLAIR images
any new ischemic lesions
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* High risk of hemorrhagic stroke (history of intracranial hemorrhage or imaging evidence of previous intracranial hemorrhage)
* Informed consent
Exclusion Criteria
* Bleeding tendency
* Pregnant or breast-feeding woman
* Hemorrhagic stroke within 6 months
* Patient who was taking antithrombotic medication other than aspirin and does not agree to change the previous medication
* Severe cardiovascular disease such as cardiomyopathy or congestive heart failure
* Life expectancy less than one year
* Contraindication to long term aspirin use
* Enrolled in other clinical trial within 30 days
20 Years
ALL
No
Sponsors
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Korea Otsuka Pharmaceutical Co., Ltd.
INDUSTRY
Asan Medical Center
OTHER
Responsible Party
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Sun U. Kwon
Professor
Principal Investigators
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Sun U. Kwon, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Departement of Neurology, Asan Medical Center
Locations
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Pamela Youde Nethersole Eastern Hospital
Hong Kong, Hong Kong, China
Queen Elizabeth Hospital
Hong Kong, Hong Kong, China
United Christian Hospital
Hong Kong, Hong Kong, China
Prince of Wales Hospital
Shatin, NT, Hong Kong, China
Manila Doctors Hospital
Manila, , Philippines
University of Santo Tomas
Manila, , Philippines
The Medical City
Pasig, , Philippines
St. Luke's Medical Center
Quezon City, , Philippines
Wallace Memorial Baptist Hospital
Busan, Busan, South Korea
Soonchunhyang University Cheonan Hospital
Cheonan, Chungcheongnam-do, South Korea
Keimyung University Dongsan Center
Daegu, Daegu, South Korea
Daegu Fatima Hospital
Daegu, Daegu, South Korea
Kangwon National University Hospital
Chuncheon, Gangwon-do, South Korea
Wonju Christian Hospital
Wŏnju, Gangwon-do, South Korea
Kwandong University College of Medicine Myongji Hospital
Gyeonggi-do, Goyang, South Korea
Gyeongsang National University Hospital
Jinju, Gyengsangnam-do, South Korea
Korea University Ansan Hospital
Ansan, Gyeonggi-do, South Korea
Soonchunhyang University Bucheon Hospital
Bucheon-si, Gyeonggi-do, South Korea
Inje University Ilsan Paik Hospital
Goyang-si, Gyeonggi-do, South Korea
National Health Insurance Corporation Ilsan Hoapital
Goyang-si, Gyeonggi-do, South Korea
Hanyang University Guri Hospital
Guri-si, Gyeonggi-do, South Korea
Bundang Medical Center, CHA University
Seongnam-si, Gyeonggi-do, South Korea
Uijeongbu St. Mary's Hospital
Uijeongbu-si, Gyeonggi-do, South Korea
Samsung changwon Medical Center
Changwon, Gyeongsangnam-do, South Korea
Wonkwang University Hospital
Iksan, Jeollabuk-do, South Korea
Chonbuk National University Hospital
Jeonju, Jeollabuk-do, South Korea
Chang Won Fatima hospital
Changwon, Kyeongsangnam-do, South Korea
Dongguk University International Hospital
Goyang, Kyoungki-do, South Korea
Hallym University Sacred Heart Hospital
Anyang, Kyunggi, South Korea
Seoul National University Bundang Hospital
Seongnam, Kyunggi, South Korea
Ajou University Hospital
Suwon, Kyunggi, South Korea
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, South Korea
Kosin University Gospel Hospital
Busan, , South Korea
Inje University Pusan Paik Hospital
Busan, , South Korea
Pusan National University Hospital
Busan, , South Korea
Dong-A University Hospital
Busan, , South Korea
Eulji University Hospital
Daejeon, , South Korea
Dongsan Medical Center
Deagu, , South Korea
Kyungpook National University Hospital
Deagu, , South Korea
Yeungnam University Medical Center
Deagu, , South Korea
Deagu Catholic University Hospital
Deagu, , South Korea
Chungnam National University Hospital
Deajeon, , South Korea
Deajeon St.Mary's Hospital, The Catholic University of Korea
Deajeon, , South Korea
Chosun University Hospital
Gwangju, , South Korea
Chonnam National University Hospital
Gwangju, , South Korea
Gachon University Gil Hoapital
Incheon, , South Korea
Inha University Hospital
Inchon, , South Korea
National Medical Center
Seoul, , South Korea
Kangbuk Samsung Hospital
Seoul, , South Korea
Severance Hospital
Seoul, , South Korea
Kyung Hee University Medical Center
Seoul, , South Korea
Hanyang University Medical Center
Seoul, , South Korea
Kangdong Sacred Heart Hospital, Hallym University
Seoul, , South Korea
Gangnam Severance Hospital
Seoul, , South Korea
Seoul Medical Center
Seoul, , South Korea
Korea University Anam Hospital
Seoul, , South Korea
Seoul St.Mary's Hospital
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Inje University Sanggye Paik Hospital
Seoul, , South Korea
Konkuk Univ. Hospital
Seoul, , South Korea
St. Mary's Hospital
Seoul, , South Korea
Hangang Sacred Heart Hospital
Seoul, , South Korea
Kangnam Sacred Heart Hospital, Hallym University College of Medicine
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
Seoul National University Borame Hospital
Seoul, , South Korea
Ewha Womans University Medical Center
Seoul, , South Korea
Eulji Hospital
Seoul, , South Korea
Chung-Ang University Medical Center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Soonchunhyang University Hospital
Seoul, , South Korea
Ulsan University Hospital
Ulsan, , South Korea
Countries
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References
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Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.
Park JH, Lee J, Kwon SU, Sung Kwon H, Hwan Lee M, Kang DW. Elevated Pulse Pressure and Recurrent Hemorrhagic Stroke Risk in Stroke With Cerebral Microbleeds or Intracerebral Hemorrhage. J Am Heart Assoc. 2022 Feb;11(3):e022317. doi: 10.1161/JAHA.121.022317. Epub 2021 Nov 15.
Cho KH, Kwon SU, Lee JS, Yu S, Cho AH. Newly diagnosed diabetes has high risk for cardiovascular outcome in ischemic stroke patients. Sci Rep. 2021 Jun 21;11(1):12929. doi: 10.1038/s41598-021-92349-y.
Park HK, Lee JS, Kim BJ, Park JH, Kim YJ, Yu S, Hwang YH, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Kwon SU, Hong KS; PICASSO investigators. Cilostazol versus aspirin in ischemic stroke with cerebral microbleeds versus prior intracerebral hemorrhage. Int J Stroke. 2021 Dec;16(9):1019-1030. doi: 10.1177/1747493020941273. Epub 2020 Jul 14.
Lee EJ, Kwon SU, Park JH, Kim YJ, Hong KS, Yu S, Hwang YH, Lee JS, Lee J, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Kim HY, Kim EG, Kim SH, Cha JK, Park MS, Nam HS, Kang DW; PICASSO Investigators. Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial. J Stroke. 2020 Jan;22(1):108-118. doi: 10.5853/jos.2019.02551. Epub 2020 Jan 31.
Kim BJ, Kwon SU, Park JH, Kim YJ, Hong KS, Wong LKS, Yu S, Hwang YH, Lee JS, Lee J, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Navarro JC, Kim HY, Kim EG, Kim S, Cha JK, Park MS, Nam HS, Kang DW; PICASSO Investigators. Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial. Stroke. 2020 Mar;51(3):931-937. doi: 10.1161/STROKEAHA.119.023855. Epub 2019 Dec 20.
Kim BJ, Lee EJ, Kwon SU, Park JH, Kim YJ, Hong KS, Wong LKS, Yu S, Hwang YH, Lee JS, Lee J, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Navarro JC, Kang DW; PICASSO investigators. Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet Neurol. 2018 Jun;17(6):509-518. doi: 10.1016/S1474-4422(18)30128-5.
Park TH, Lee JS, Park SS, Ko Y, Lee SJ, Lee KB, Lee J, Kang K, Park JM, Choi JC, Kim DE, Cho YJ, Kim JT, Kim DH, Cha JK, Han MK, Lee J, Oh MS, Yu KH, Lee BC, Bae HJ, Hong KS. Safety and efficacy of intravenous recombinant tissue plasminogen activator administered in the 3- to 4.5-hour window in Korea. J Stroke Cerebrovasc Dis. 2014 Aug;23(7):1805-12. doi: 10.1016/j.jstrokecerebrovasdis.2014.04.027. Epub 2014 Jun 21.
Other Identifiers
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PICASSO
Identifier Type: -
Identifier Source: org_study_id