Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II (TOSS-2)

January 4, 2010 updated by: Asan Medical Center

Trial for Efficacy and Safety of Cilostazol on the Progression of Symptomatic Intracranial Stenosis Comparing Clopidogrel

This study will recruit 480 acute stroke patients with symptomatic intracranial stenosis (M1 segment of Middle cerebral artery (MCA) or basilar artery).

They will be randomly assigned into cilostazol group or clopidogrel group. Every patients will take 100mg of aspirin a day additionally.

The primary outcome variable of this study is Progression rate of symptomatic intracranial stenosis on magnetic resonance angiogram (MRA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

[Goal] To Reveal the Effect and Safety of Cilostazol Compared with Clopidogrel on the Prevention of the Progression of Symptomatic Intracranial Arterial Stenosis.

[Trial Design] Double-Blind, Active-Controlled, Randomized, Multicenter Trial

[Participants] Acute ischemic stroke patients with symptomatic intracranial arterial stenosis

[Methods]

  • Double-Blind, Active-Controlled, Randomized, Multicenter Trial
  • Investigational product (Double Dummy Method):

Cilostazol 200mg (100mg twice per day) versus clopidogrel 75mg

  • Concomitant medication: Aspirin 100 (75-150) mg per day
  • Medication Duration: 7 months

[Outcome Variables]

Primary Outcome Variable:

  • Progression rate of symptomatic intracranial arterial stenosis

Secondary outcome variables:

  • The occurrence of new MRI (magnetic resonance image) lesion on follow-up MRI
  • Stroke events
  • Overall cardiovascular events: stroke, acute coronary syndrome, vascular death
  • Ipsilateral ischemic stroke rate
  • Fatal or major bleeding complications

Study Type

Interventional

Enrollment (Actual)

457

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Hong Kong, Hong Kong
        • Prince of Wales Hospital
  • Korea, Republic of
      • Inchon, Korea, Republic of, 400-103
        • Inha University Hospital
      • Seongnam, Korea, Republic of
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 134-701
        • Kangdong Sacred Heart Hospital, Hallym University
      • Seoul, Korea, Republic of, 140-743
        • Soonchunhyang University Hospital
      • Seoul, Korea, Republic of, 156-707
        • Seoul National University Boramae Hospital
      • Seoul, Korea, Republic of, 280-1
        • Eulji Hospital
    • Gwangjin-gu Hwayang-dong
      • Seoul, Gwangjin-gu Hwayang-dong, Korea, Republic of, 143-729
        • Konkuk Univ. Hospital
    • Gyeonggi-do
      • Goyang, Gyeonggi-do, Korea, Republic of, 411-706
        • Inje University Ilsan Paik Hospital
    • Kyoungki-do
      • Goyang, Kyoungki-do, Korea, Republic of, 410-773
        • Dongguk University International Hospital
    • Kyunggi
      • Anyang, Kyunggi, Korea, Republic of, 430-070
        • Hallym University Sacred Heart Hospital
  • Philippines
      • Manila, Philippines
        • Philippine General Hospital
      • Manila, Philippines
        • University of Santo Tomas Hospital
  • Thailand
      • Bangkok, Thailand
        • Siriraj Hospital
      • Bangkok, Thailand
        • Ramathibodi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Cerebral infarction within 2 weeks from the onset or TIA with corresponding acute ischemic brain lesions on MRI within 2 weeks from the onset
  • Age: more than 35 years of age
  • Patient with significant focal stenosis in the M1 segment of middle cerebral artery (MCA) or basilar artery (BA) with acute ischemic lesions on magnetic resonance imaging (MRI) within the vascular territory of the stenosed artery.

Exclusion Criteria:

  • Patients with any contraindications to the treatment with antiplatelet therapy
  • Patients with potential cardiac embolic source; prosthetic valve, atrial fibrillation, atrial flutter, left atrial/atrial appendage thrombus, sick sinus syndrome, left ventricular thrombus, dilated cardiomyopathy, akinetic or hypokinetic left ventricular segment, atrial myxoma, Infective endocarditis, mitral valve stenosis or prolapse, mitral annuls calcification, left atrial turbulence, nonbacterial endocarditis, congestive heart failure, recent myocardial infarction (within 4 weeks)
  • Patients with more than 50% stenosis in the parent artery of symptomatic stenosis
  • Bleeding diathesis
  • Chronic liver disease (ALT > 100 or AST > 100) or chronic renal disease (creatinine > 3.0mg/dl)
  • Anemia (hemoglobin < 10mg/dl) or thrombocytopenia (platelet count less than 100,000/mm3)
  • Nonatherosclerotic vasculopathy; patients with clinical characteristics suggesting arterial dissection, moyamoya disease, Takayasu's arteritis, radiation associated angiopathy, and other vasculitis.
  • Severe stroke: NIH stroke scale : more than 16
  • Pregnant or lactating patients
  • Chronic user of NSAIDs
  • Thrombolytic therapy for the symptomatic stenosis
  • Symptomatic stenosis scheduled for angioplasty
  • Patients with pacemaker or any other contraindications to MRI

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cilostazol
cilostazol 100mg bid plus placebo of clopidogrel
Drug: Cilostazol
Cilostazol 100mg twice a day plus placebo of clopidogrel once a day
Other Names:
  • cilostazol produced by Korea Otsuka Pharmaceutical
Active Comparator: Clopidogrel
clopidogrel 75mg qd and matching placebo of cilostazol
Drug: clopidogrel
Clopidogrel 75mg once a day plus placebo of cilostazol twice a day
Other Names:
  • Plavix, produced by Sanofi-Aventis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Progression of Symptomatic Intracranial Stenosis
Time Frame: 7 months after treatment

Blind reviewers classified the presence and severity of stenosis on middle cerebral arteries and basilar artery on magnetic resonance angiogram (MRA) into 5 grades; normal, mild, moderate, severe and occlusion. Progression was defined as worsening of stenosis by 1 or more grades on final MRA as compared with the baseline MRA.

The progression of symptomatic stenosis is defined as 1 or more grade worsening of the stenosis on the symptomatic artery on MRA.
7 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI
Time Frame: 7 months after treatment
number of patients with new ischemic lesions on FLAIR (Fluid attenuation inversion recovery) images of follow-up MRI, which were determined by slice to slice comparison with baseline MRI.
7 months after treatment
Number of Participants With Stroke Events
Time Frame: upto 7 months after randomization
including nonfatal ischemic stroke, nonfatal hemorrhagic stroke and fatal stroke
upto 7 months after randomization
Number of Participants With Overall Cardiovascular Events
Time Frame: upto 7 months after randomization
including nonfatal stroke, nonfatal myocardial infarction and vascular death.
upto 7 months after randomization
Number of Patients With Ipsilateral Ischemic Stroke Rate
Time Frame: upto 7 months after randomization
ischemic stroke event which occured in the vascular territory of initial symptomatic stenosis
upto 7 months after randomization
Numbers of Fatal or Major Bleeding Complications
Time Frame: upto 7 months after randomization
life-threatening or fatal bleeding was defined as any fatal bleeding event, a drop in hemoglobin of ≥ 50g/L, or significant hypotension with need for inotropic agents, symptomatic intracranial hemorrhage, or transfusion of ≥ 4 units of red-blood cells or equivalent amount of whole blood. Major bleeding was defined as significantly disabling bleedings, intraocular bleeding leading to significant visual loss, or bleeding requiring transfusion of ≤ 3 units of red-blood cells or equivalent amount of whole blood
upto 7 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Collaborators

Korea Otsuka International Asia Arab

Investigators

  • Principal Investigator: Sun U. Kwon, MD, PhD, Asan Medical Center, Univsersity of Ulsan, Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

August 11, 2005

First Submitted That Met QC Criteria

August 12, 2005

First Posted (Estimate)

August 15, 2005

Study Record Updates

Last Update Posted (Estimate)

January 12, 2010

Last Update Submitted That Met QC Criteria

January 4, 2010

Last Verified

November 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOSS-2

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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