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Brain IschemiaPhase 4PICASSONCT01013532

PreventIon of CArdiovascular Events in iSchemic Stroke Patients With High Risk of Cerebral HemOrrhage

A Phase 4 study testing Cilostazol, Probucol and Aspirin in people with Brain Ischemia and Intracranial Hemorrhages, run by Asan Medical Center at 71 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Through this study, the investigators are to prove that Cilostazol effectively prevent cardiovascular events in ischemic stroke patients with high risk of cerebral hemorrhage, along with no significant increase in the risk of occurrence of hemorrhagic side effects. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Brain Ischemia, Intracranial Hemorrhages
What is being tested?
Cilostazol, Probucol and Aspirin
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,600 participants
Where
71 sitesin 3 countries
Study dates
Jun 2009to Dec 2016
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with transient ischemic attack (TIA) or ischemic stroke within 180 days prior to screening - Adult aged 20 years or older
  • High risk of hemorrhagic stroke (history of intracranial hemorrhage or imaging evidence of previous intracranial hemorrhage)
  • Informed consent

Who cannot join

  • Clinical diagnosis of myocardial infarction or coronary intervention within 4 weeks
  • 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
Show all 9Show fewer
  • Life expectancy less than one year
  • Contraindication to long term aspirin use
  • Enrolled in other clinical trial within 30 days

Trial locations and contacts

71 sites in 3 countries.

71 sites in 3 countries

South Korea63 sites

  • Korea University Ansan Hospital

    Ansan, Gyeonggi-do, 152-703

  • Hallym University Sacred Heart Hospital

    Anyang, Kyunggi, 430-070

  • Soonchunhyang University Bucheon Hospital

    Bucheon-si, Gyeonggi-do, 420-020

  • Wallace Memorial Baptist Hospital

    Busan, Busan, 609-728

  • Kosin University Gospel Hospital

    Busan, 602-702

  • Inje University Pusan Paik Hospital

    Busan, 614-735

  • Pusan National University Hospital

    Busan, 626-770

  • Dong-A University Hospital

    Busan

  • Samsung changwon Medical Center

    Changwon, Gyeongsangnam-do, 630-723

  • Chang Won Fatima hospital

    Changwon, Kyeongsangnam-do, 641-560

  • Soonchunhyang University Cheonan Hospital

    Cheonan, Chungcheongnam-do, 330-721

  • Chungbuk National University Hospital

    Cheongju-si, North Chungcheong, 361-711

  • Kangwon National University Hospital

    Chuncheon, Gangwon-do, 200-947

  • Keimyung University Dongsan Center

    Daegu, Daegu, 700-712

  • Daegu Fatima Hospital

    Daegu, Daegu, 701-600

  • Eulji University Hospital

    Daejeon, 302-799

  • Dongsan Medical Center

    Deagu, 700-712

  • Kyungpook National University Hospital

    Deagu, 700-721

  • Yeungnam University Medical Center

    Deagu, 705-717

  • Deagu Catholic University Hospital

    Deagu, 705-718

  • Chungnam National University Hospital

    Deajeon, 301-721

  • Deajeon St.Mary's Hospital, The Catholic University of Korea

    Deajeon, 303-723

  • Dongguk University International Hospital

    Goyang, Kyoungki-do, 410-773

  • Inje University Ilsan Paik Hospital

    Goyang-si, Gyeonggi-do, 411-706

  • National Health Insurance Corporation Ilsan Hoapital

    Goyang-si, Gyeonggi-do, 411-719

  • Hanyang University Guri Hospital

    Guri-si, Gyeonggi-do, 471-701

  • Chosun University Hospital

    Gwangju, 501-717

  • Chonnam National University Hospital

    Gwangju, 501-757

  • Kwandong University College of Medicine Myongji Hospital

    Gyeonggi-do, Goyang, 412-270

  • Wonkwang University Hospital

    Iksan, Jeollabuk-do, 570-711

  • Gachon University Gil Hoapital

    Incheon, 405-760

  • Inha University Hospital

    Inchon, 400-103

  • Chonbuk National University Hospital

    Jeonju, Jeollabuk-do, 561-712

  • Gyeongsang National University Hospital

    Jinju, Gyengsangnam-do, 660-702

  • Seoul National University Bundang Hospital

    Seongnam, Kyunggi

  • Bundang Medical Center, CHA University

    Seongnam-si, Gyeonggi-do, 463-712

  • National Medical Center

    Seoul, 100-799

  • Kangbuk Samsung Hospital

    Seoul, 110-746

  • Severance Hospital

    Seoul, 120-752

  • Kyung Hee University Medical Center

    Seoul, 130-702

  • Hanyang University Medical Center

    Seoul, 133-792

  • Kangdong Sacred Heart Hospital, Hallym University

    Seoul, 134-701

  • Gangnam Severance Hospital

    Seoul, 135-720

  • Seoul Medical Center

    Seoul, 135-740

  • Korea University Anam Hospital

    Seoul, 136-705

  • Seoul St.Mary's Hospital

    Seoul, 137-701

  • Asan Medical Center

    Seoul, 138-736

  • Inje University Sanggye Paik Hospital

    Seoul, 139-707

  • Konkuk Univ. Hospital

    Seoul, 143-729

  • St. Mary's Hospital

    Seoul, 150-713

  • Hangang Sacred Heart Hospital

    Seoul, 150-719

  • Kangnam Sacred Heart Hospital, Hallym University College of Medicine

    Seoul, 150-950

  • Korea University Guro Hospital

    Seoul, 152-703

  • Seoul National University Borame Hospital

    Seoul, 156-707

  • Ewha Womans University Medical Center

    Seoul, 158-710

  • Eulji Hospital

    Seoul, 280-1

  • Chung-Ang University Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Soonchunhyang University Hospital

    Seoul

  • Ajou University Hospital

    Suwon, Kyunggi

  • Uijeongbu St. Mary's Hospital

    Uijeongbu-si, Gyeonggi-do, 480-821

  • Ulsan University Hospital

    Ulsan

  • Wonju Christian Hospital

    Wŏnju, Gangwon-do, 220-701

Other trials in South Korea

China4 sites

  • Pamela Youde Nethersole Eastern Hospital

    Hong Kong, Hong Kong

  • Queen Elizabeth Hospital

    Hong Kong, Hong Kong

  • United Christian Hospital

    Hong Kong, Hong Kong

  • Prince of Wales Hospital

    Shatin, NT, Hong Kong

Other trials in China

Philippines4 sites

  • Manila Doctors Hospital

    Manila

  • University of Santo Tomas

    Manila

  • The Medical City

    Pasig

  • St. Luke's Medical Center

    Quezon City

Other trials in Philippines

About this study

Official title: A Multicenter, Double Blind, Factorial Design, Phase IV Trial to Compare the Efficacy and Safety of Cilostazol Long-term Treatment With Aspirin in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage for the Prevention of Cerebral Hemorrhage and Cardiovascular Events and to Compare the Preventive Effect of Probucol in the Same Patient Group With Non-drug User Group for the Prevention of Cardiovascular Events

Through this study, the investigators are to prove that Cilostazol effectively prevent cardiovascular events in ischemic stroke patients with high risk of cerebral hemorrhage, along with no significant increase in the risk of occurrence of hemorrhagic side effects.

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.

Read the detailed description

It has been generally accepted that 'old age' and 'hypertension' may be risk factors not only for cerebral infarction but also for cerebral hemorrhage. Usually 40 to 60 percent of recurrent strokes after cerebral hemorrhage cases are cerebral infarction; and 5 to 10 percent of recurrent stroke after cerebral infarction cases are cerebral hemorrhage.

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.
Being tested
Cilostazol, Probucol, Aspirin, placebo of cilostazol, placebo of aspirin
Keywords
Ischemic Stroke, Intracranial Hemorrhage, Cilostazol, Probucol
Medical subject headings
Brain Ischemia, Intracranial Hemorrhages, Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CilostazolDrug

    Also called Pletaal produced by Korea Otsuka Pharmaceutical company

    Cilostazol 100mg bid

  • ProbucolDrug

    Also called Probucol is produced by Otsuka Pharmaceutical

    Probucol 250mg bid

  • AspirinDrug

    Aspirin 100mg qd

  • placebo of cilostazolDrug

    same shape and size of active cilostazol

  • placebo of aspirinDrug

    same size and shape of active aspirin 100mg

  • ankle-brachial index (ABI)Device

    measurement of ABI every years during follow up

  • intima-medial thickness (IMT)Device

    Also called change of maximal IMT and mean IMT

    ultrasound measured IMT of both common carotid arteries

  • new asymptomatic brain hemorrhageDevice

    asymptomatic macrobleedings or microbleedings on GRE images

  • new ischemic lesions on follow-up FLAIR imagesDevice

    any new ischemic lesions

Study groups in NCT01013532
Study groupRoleWhat they receive
Cilostazol+ ProbucolExperimental100mg cilostazol bid plus probucol plus placebo of aspirin
Receives: Drug: Cilostazol; Drug: Probucol; Drug: placebo of aspirin; Device: ankle-brachial index (ABI); Device: intima-medial thickness (IMT); Device: new asymptomatic brain hemorrhage; Device: new ischemic lesions on follow-up FLAIR images
Aspirin + ProbucolActive comparatoraspirin plus placebo cilostazol plus probucol
Receives: Drug: Probucol; Drug: Aspirin; Drug: placebo of cilostazol; Device: ankle-brachial index (ABI); Device: intima-medial thickness (IMT); Device: new asymptomatic brain hemorrhage; Device: new ischemic lesions on follow-up FLAIR images
CilostazolExperimentalcilostazol plus placebo of aspirin
Receives: Drug: Cilostazol; Drug: placebo of aspirin; Device: ankle-brachial index (ABI); Device: intima-medial thickness (IMT); Device: new asymptomatic brain hemorrhage; Device: new ischemic lesions on follow-up FLAIR images
AspirinActive comparatoraspirin plus placebo of cilostazol
Receives: Drug: Aspirin; Drug: placebo of cilostazol; Device: ankle-brachial index (ABI); Device: intima-medial thickness (IMT); Device: new asymptomatic brain hemorrhage; Device: new ischemic lesions on follow-up FLAIR images

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to the first occurrence of cerebral hemorrhage

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

  2. Time to the first occurence of composite cardiovascular events

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

Secondary outcomes (4)

  1. Time to the first occurrence of stroke

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

  2. Time to the first occurrence of ischemic stroke

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

  3. Time to the first occurence of myocardial infarction

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

  4. Time to the first occurence of other designated vascular events

    Measured: time since randomization; follow-up period is 1.0 to 5.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionSep 2016 (estimated)
  4. Study completionDec 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01013532
Sponsor's protocol ID
PICASSO
Acronym
PICASSO
Status last verified
Dec 2015
First submitted
10 Nov 2009
Last updated
24 Dec 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36700520

  • 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.

    PubMed 34779245

  • 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.

    PubMed 34155277

  • 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.

    PubMed 32664827

  • 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.

    PubMed 32027796

  • 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.

    PubMed 31856691

  • 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.

    PubMed 29778364

  • 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.

    PubMed 24957314

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cilostazol, Probucol and Aspirin in people with Brain Ischemia and Intracranial Hemorrhages, run by Asan Medical Center at 71 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in South Korea, China, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to the first occurrence of cerebral hemorrhage (time frame: time since randomization; follow-up period is 1.0 to 5.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01013532, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2015.

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