Trial Outcomes & Findings for Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II (NCT NCT00130039)
NCT ID: NCT00130039
Last Updated: 2010-01-12
Results Overview
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.
COMPLETED
PHASE4
457 participants
7 months after treatment
2010-01-12
Participant Flow
507 patients were registered www.toss2.com from 20 centers of 4 countries (Korea, Hongkong, Thailand, Philippines). 50 patients were excluded during case verification process because they did not satisfy patient's eligibility criteria. finally 457 patients were randomized into cilostazol or clopidogrel group
The excluded patients did not satisfy the definition of the symptomatic stenosis of our study protocol.
Participant milestones
| Measure |
Cilostazol
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Overall Study
STARTED
|
232
|
225
|
|
Overall Study
COMPLETED
|
202
|
207
|
|
Overall Study
NOT COMPLETED
|
30
|
18
|
Reasons for withdrawal
| Measure |
Cilostazol
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
15
|
11
|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
|
Overall Study
Adverse Event
|
4
|
2
|
|
Overall Study
Physician Decision
|
3
|
0
|
|
Overall Study
clinical events without follow up MRI
|
5
|
4
|
Baseline Characteristics
Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II
Baseline characteristics by cohort
| Measure |
Cilostazol
n=232 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
Total
n=457 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
93 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
205 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
139 Participants
n=5 Participants
|
113 Participants
n=7 Participants
|
252 Participants
n=5 Participants
|
|
Age Continuous
|
66.42 years
STANDARD_DEVIATION 11.33 • n=5 Participants
|
64.58 years
STANDARD_DEVIATION 11.11 • n=7 Participants
|
65.52 years
STANDARD_DEVIATION 11.24 • n=5 Participants
|
|
Sex: Female, Male
Female
|
110 Participants
n=5 Participants
|
113 Participants
n=7 Participants
|
223 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
122 Participants
n=5 Participants
|
112 Participants
n=7 Participants
|
234 Participants
n=5 Participants
|
|
Region of Enrollment
Philippines
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Hong Kong
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
210 participants
n=5 Participants
|
203 participants
n=7 Participants
|
413 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 months after treatmentBlind 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.
Outcome measures
| Measure |
Cilostazol
n=202 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=207 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Number of Participants With Progression of Symptomatic Intracranial Stenosis
|
20 participants
|
32 participants
|
SECONDARY outcome
Timeframe: 7 months after treatmentPopulation: this analysis included the patients who had performed follow-up FLAIR imaging
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.
Outcome measures
| Measure |
Cilostazol
n=182 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=191 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Number of Participants With New MRI (Magnetic Resonance Image) Lesions on Follow-up MRI
|
34 pariticipants
|
23 pariticipants
|
SECONDARY outcome
Timeframe: upto 7 months after randomizationPopulation: this outcome analysis performed on the intention to treat (ITT) method
including nonfatal ischemic stroke, nonfatal hemorrhagic stroke and fatal stroke
Outcome measures
| Measure |
Cilostazol
n=232 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Number of Participants With Stroke Events
|
11 participants
|
7 participants
|
SECONDARY outcome
Timeframe: upto 7 months after randomizationPopulation: this outcome analysis was done intention to treat method
including nonfatal stroke, nonfatal myocardial infarction and vascular death.
Outcome measures
| Measure |
Cilostazol
n=232 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Number of Participants With Overall Cardiovascular Events
|
15 participants
|
10 participants
|
SECONDARY outcome
Timeframe: upto 7 months after randomizationPopulation: this outcome analysis was done ITT method
ischemic stroke event which occured in the vascular territory of initial symptomatic stenosis
Outcome measures
| Measure |
Cilostazol
n=232 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Number of Patients With Ipsilateral Ischemic Stroke Rate
|
9 participants
|
5 participants
|
SECONDARY outcome
Timeframe: upto 7 months after randomizationPopulation: this outcome analysis was done ITT method
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
Outcome measures
| Measure |
Cilostazol
n=232 Participants
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 Participants
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Numbers of Fatal or Major Bleeding Complications
|
2 events
|
6 events
|
Adverse Events
Cilostazol
Clopidogrel
Serious adverse events
| Measure |
Cilostazol
n=232 participants at risk
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 participants at risk
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Gastrointestinal disorders
'Blood tinged loose stool
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Infections and infestations
multi-organ failure
|
0.00%
0/232
|
0.44%
1/225 • Number of events 1
|
|
Nervous system disorders
abnormal involuntary movement
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
acute bronchitis
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Cardiac disorders
acute myocardial infarction
|
1.3%
3/232 • Number of events 3
|
1.3%
3/225 • Number of events 3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
cancer
|
0.86%
2/232 • Number of events 2
|
0.44%
1/225 • Number of events 1
|
|
Nervous system disorders
cerebral infarction
|
4.3%
10/232 • Number of events 10
|
2.7%
6/225 • Number of events 6
|
|
Nervous system disorders
cerebral hemorrhage
|
0.43%
1/232 • Number of events 1
|
0.44%
1/225 • Number of events 1
|
|
Vascular disorders
aneurysm unruptured
|
0.86%
2/232 • Number of events 2
|
0.00%
0/225
|
|
Gastrointestinal disorders
gastroenteritis
|
2.2%
5/232 • Number of events 5
|
2.2%
5/225 • Number of events 5
|
|
Cardiac disorders
cardiac arrest
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Gastrointestinal disorders
GI bleeding
|
0.86%
2/232 • Number of events 2
|
2.7%
6/225 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
traffic accident
|
0.00%
0/232
|
0.44%
1/225 • Number of events 1
|
|
Ear and labyrinth disorders
otitis media
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Renal and urinary disorders
cystitis
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Eye disorders
cataract operation
|
0.00%
0/232
|
1.3%
3/225 • Number of events 3
|
|
Psychiatric disorders
depression
|
2.6%
6/232 • Number of events 6
|
1.8%
4/225 • Number of events 4
|
|
Endocrine disorders
diabetes complications
|
0.86%
2/232 • Number of events 2
|
1.8%
4/225 • Number of events 4
|
|
Nervous system disorders
general weakness
|
0.43%
1/232 • Number of events 1
|
1.3%
3/225 • Number of events 3
|
|
Ear and labyrinth disorders
vestibular neuronitis
|
0.00%
0/232
|
0.44%
1/225 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
fracture or other joint pain
|
1.7%
4/232 • Number of events 4
|
3.1%
7/225 • Number of events 7
|
|
Infections and infestations
infection
|
0.43%
1/232 • Number of events 1
|
0.89%
2/225 • Number of events 2
|
|
Nervous system disorders
headache
|
1.3%
3/232 • Number of events 3
|
0.44%
1/225 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
edema
|
0.86%
2/232 • Number of events 2
|
0.44%
1/225 • Number of events 1
|
|
Cardiac disorders
tachycardia
|
0.86%
2/232 • Number of events 2
|
0.44%
1/225 • Number of events 1
|
|
Nervous system disorders
seizure
|
0.43%
1/232 • Number of events 1
|
0.00%
0/225
|
|
Cardiac disorders
severe hypertension
|
0.43%
1/232 • Number of events 1
|
0.44%
1/225 • Number of events 1
|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/232
|
0.89%
2/225 • Number of events 2
|
Other adverse events
| Measure |
Cilostazol
n=232 participants at risk
cilostazol 100mg twice a day plus placebo of clopidogrel
|
Clopidogrel
n=225 participants at risk
clopidogrel 75mg per day and matching placebo of cilostazol
|
|---|---|---|
|
Nervous system disorders
headache
|
26.7%
62/232 • Number of events 78
|
15.6%
35/225 • Number of events 42
|
|
Gastrointestinal disorders
diarrhea
|
6.9%
16/232 • Number of events 18
|
4.0%
9/225 • Number of events 10
|
|
Blood and lymphatic system disorders
petechia
|
0.00%
0/232
|
1.3%
3/225 • Number of events 3
|
|
Nervous system disorders
dizziness
|
12.1%
28/232 • Number of events 29
|
9.3%
21/225 • Number of events 23
|
|
Cardiac disorders
palpitation
|
3.0%
7/232 • Number of events 7
|
1.3%
3/225 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
urticaria
|
0.86%
2/232 • Number of events 2
|
1.3%
3/225 • Number of events 3
|
|
Gastrointestinal disorders
epigastric soreness
|
6.5%
15/232 • Number of events 16
|
4.4%
10/225 • Number of events 10
|
|
Gastrointestinal disorders
GI bleedings
|
1.3%
3/232 • Number of events 3
|
0.00%
0/225
|
|
Social circumstances
others
|
72.8%
169/232 • Number of events 565
|
100.0%
225/225 • Number of events 564
|
Additional Information
Sun U. Kwon, MD, PhD, Prof
Asan Medical Center, University of Ulsan
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place