Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II

NCT00130039 | Completed Phase 4 Results DMC

• 1 other identifier: TOSS-2
• Study Type: interventional
• Target: 457
• Locations: 4 countries
• Sites: 19

Brief Summary

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).

Conditions

Cerebral Infarction; Atherosclerosis

Keywords

Infarction, Cerebral; cilostazol; stenosis; atherosclerosis; clopidogrel

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression of Symptomatic Intracranial Stenosis

  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 Outcomes (5)

• Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI

  7 months after treatment

• Number of Participants With Stroke Events

  upto 7 months after randomization

• Number of Participants With Overall Cardiovascular Events

  upto 7 months after randomization

• Number of Patients With Ipsilateral Ischemic Stroke Rate

  upto 7 months after randomization

• Numbers of Fatal or Major Bleeding Complications

  upto 7 months after randomization

Study Arms (2)

cilostazol

EXPERIMENTAL

cilostazol 100mg bid plus placebo of clopidogrel

Drug: Cilostazol

Clopidogrel

ACTIVE COMPARATOR

clopidogrel 75mg qd and matching placebo of cilostazol

Drug: clopidogrel

Interventions

clopidogrel DRUG

Clopidogrel 75mg once a day plus placebo of cilostazol twice a day

Also known as: Plavix, produced by Sanofi-Aventis.

Clopidogrel

Cilostazol DRUG

Cilostazol 100mg twice a day plus placebo of clopidogrel once a day

Also known as: cilostazol produced by Korea Otsuka Pharmaceutical

cilostazol

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead
• Korea Otsuka International Asia Arab: collaborator

Study Sites (19)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Philippine General Hospital

Manila, Philippines

Location

University of Santo Tomas Hospital

Manila, Philippines

Location

Konkuk Univ. Hospital

Seoul, Gwangjin-gu Hwayang-dong, 143-729, South Korea

Location

Inje University Ilsan Paik Hospital

Goyang-si, Gyeonggi-do, 411-706, South Korea

Location

Dongguk University International Hospital

Goyang, Kyoungki-do, 410-773, South Korea

Location

Hallym University Sacred Heart Hospital

Anyang, Kyunggi, 430-070, South Korea

Location

Soonchunhyang University Hospital

Seoul, Seoul, 140-743, South Korea

Location

Inha University Hospital

Inchon, 400-103, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Kangdong Sacred Heart Hospital, Hallym University

Seoul, 134-701, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Seoul National University Boramae Hospital

Seoul, 156-707, South Korea

Location

Eulji Hospital

Seoul, 280-1, South Korea

Location

Ramathibodi Hospital

Bangkok, Thailand

Location

Siriraj Hospital

Bangkok, Thailand

Location

Related Publications (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.

  PMID: 24957314 DERIVED

• Kim BJ, Rha JH, Kim SR, Kim DE, Kim HY, Lee JH, Bae HJ, Han MK, Kang DW, Ratanakorn D, Kim JS, Kwon SU. The effect of cilostazol on carotid intima-media thickness progression in patients with symptomatic intracranial atherosclerotic stenosis. J Stroke Cerebrovasc Dis. 2014 May-Jun;23(5):1164-70. doi: 10.1016/j.jstrokecerebrovasdis.2013.10.007. Epub 2013 Dec 6.

  PMID: 24315720 DERIVED

• Jung JM, Kang DW, Yu KH, Koo JS, Lee JH, Park JM, Hong KS, Cho YJ, Kim JS, Kwon SU; TOSS-2 Investigators. Predictors of recurrent stroke in patients with symptomatic intracranial arterial stenosis. Stroke. 2012 Oct;43(10):2785-7. doi: 10.1161/STROKEAHA.112.659185. Epub 2012 Aug 21.

  PMID: 22910894 DERIVED

• Kim DE, Kim JY, Jeong SW, Cho YJ, Park JM, Lee JH, Kang DW, Yu KH, Bae HJ, Hong KS, Koo JS, Lee SH, Lee BC, Han MK, Rha JH, Lee YS, Kim GM, Chae SL, Kim JS, Kwon SU. Association between changes in lipid profiles and progression of symptomatic intracranial atherosclerotic stenosis: a prospective multicenter study. Stroke. 2012 Jul;43(7):1824-30. doi: 10.1161/STROKEAHA.112.653659. Epub 2012 Apr 26.

  PMID: 22539545 DERIVED

• Kwon SU, Hong KS, Kang DW, Park JM, Lee JH, Cho YJ, Yu KH, Koo JS, Wong KS, Lee SH, Lee KB, Kim DE, Jeong SW, Bae HJ, Lee BC, Han MK, Rha JH, Kim HY, Mok VC, Lee YS, Kim GM, Suwanwela NC, Yun SC, Nah HW, Kim JS. Efficacy and safety of combination antiplatelet therapies in patients with symptomatic intracranial atherosclerotic stenosis. Stroke. 2011 Oct;42(10):2883-90. doi: 10.1161/STROKEAHA.110.609370. Epub 2011 Jul 28.

  PMID: 21799173 DERIVED

MeSH Terms

Conditions

Cerebral Infarction; Atherosclerosis; Constriction, Pathologic

Interventions

Clopidogrel; Cilostazol

Condition Hierarchy (Ancestors)

Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tetrazoles; Azoles; Quinolines

Results Point of Contact

• Title: Sun U. Kwon, MD, PhD, Prof
• Organization: Asan Medical Center, University of Ulsan

sukwon@amc.seoul.kr

82-2-3010-3960

Study Officials

• Sun U. Kwon, MD, PhD

  Asan Medical Center, Univsersity of Ulsan, Medical College

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 11, 2005
• First Posted: August 15, 2005
• Study Start: August 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: January 12, 2010
• Results First Posted: January 1, 2010

Record last verified: 2009-11

Locations

KR (13); PH (2); TH (2); HK (2)