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

A

Asan Medical Center

Status and phase

Unknown
Phase 4

Conditions

Brain Ischemia
Intracranial Hemorrhages

Treatments

Drug: placebo of cilostazol
Drug: placebo of aspirin
Device: intima-medial thickness (IMT)
Device: new asymptomatic brain hemorrhage
Drug: Probucol
Drug: Aspirin
Device: new ischemic lesions on follow-up FLAIR images
Drug: Cilostazol
Device: ankle-brachial index (ABI)

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT01013532
PICASSO

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,600 estimated patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • Life expectancy less than one year
  • Contraindication to long term aspirin use
  • Enrolled in other clinical trial within 30 days

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

Quadruple Blind

1,600 participants in 4 patient groups

Cilostazol+ Probucol
Experimental group
Description:
100mg cilostazol bid plus probucol plus placebo of aspirin
Treatment:
Device: ankle-brachial index (ABI)
Device: new ischemic lesions on follow-up FLAIR images
Drug: Cilostazol
Drug: Probucol
Device: new asymptomatic brain hemorrhage
Device: intima-medial thickness (IMT)
Drug: placebo of aspirin
Aspirin + Probucol
Active Comparator group
Description:
aspirin plus placebo cilostazol plus probucol
Treatment:
Device: ankle-brachial index (ABI)
Device: new ischemic lesions on follow-up FLAIR images
Drug: Aspirin
Drug: Probucol
Device: new asymptomatic brain hemorrhage
Device: intima-medial thickness (IMT)
Drug: placebo of cilostazol
Cilostazol
Experimental group
Description:
cilostazol plus placebo of aspirin
Treatment:
Device: ankle-brachial index (ABI)
Device: new ischemic lesions on follow-up FLAIR images
Drug: Cilostazol
Device: new asymptomatic brain hemorrhage
Device: intima-medial thickness (IMT)
Drug: placebo of aspirin
Aspirin
Active Comparator group
Description:
aspirin plus placebo of cilostazol
Treatment:
Device: ankle-brachial index (ABI)
Device: new ischemic lesions on follow-up FLAIR images
Drug: Aspirin
Device: new asymptomatic brain hemorrhage
Device: intima-medial thickness (IMT)
Drug: placebo of cilostazol

Trial contacts and locations

71

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Data sourced from clinicaltrials.gov

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