Overcome Biochemical Aspirin Resistance Through Cilostazol Combination

Study Overview
=================
Brief Summary
-----------------
This study will recruit 316 ischemic stroke patients taking aspirin. They will be randomly assigned into cilostazol group or placebo group. Every patients will take 200mg of cilostazol a day or placebo for 1 month. The primary outcome variable of this study is rate of biochemical aspirin resistance on the Ultra Rapid Platelet Function Assay-ASA.

Detailed Description
-----------------
[Goal] To reveal the effect and safety of additional cilostazol for overcoming biochemical aspirin resistance. [Trial Design] Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial [Participants] Ischemic stroke patients taking aspirin [Methods] Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial Investigational product: Cilostazol 200mg (100mg twice per day) Concomitant medication: Aspirin 100 mg per day Medication Duration: 1 month [Outcome Variables] Primary Outcome Variable: • the proportion of patients with aspirin reaction units (ARUs) values ≥550 on the Ultra Rapid Platelet Function Assay-ASA Secondary outcome variables: the proportion of patients with ARUs values ≥500 on the Ultra Rapid Platelet Function Assay-ASA ARUs values Bleeding time (BT) Fatal or major bleeding complications Any bleeding complications

Official Title
-----------------
Phase 4 Study of Additional Cilostazol for Overcoming Biochemical Aspirin Resistance in the Chronic Stroke Patients

Conditions
-----------------
Cerebral Infarction

Intervention / Treatment
-----------------
* Drug: Cilostazol
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Symptomatic cerebral infarction documented on MRI or CT More than 35 years of age Patients taking aspirin 100mg a day for 2 weeks or more before randomization Exclusion Criteria: Patients taking any antiplatelets other than aspirin within 2 weeks before randomization Patients taking any anticoagulants within 2 weeks before randomization Patients taking thrombolytic therapy within 2 weeks before randomization Patients taking any NSAIDs within 2 weeks before randomization Patients who need to take NSAIDs regularly (e.g. rheumatic arthritis). 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) Pregnant or lactating patients Patients scheduled for angioplasty or revascularization procedures within 4 weeks Patients scheduled for any surgery or invasive procedures within 4 weeks Patients having acute coronary syndrome

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Cilostazol<br>100mg of Cilostazol twice a day | Drug: Cilostazol<br>* cilostazol 100mg twice a day for 4 weeks<br>* Other names: pletaal;|
| Placebo Comparator: Placebo<br>matching placebo to cilostazol | Drug: placebo<br>* placebo 1 tablet twice a day matching for cilostazol<br>* Other names: matching placebo of cilostazol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aspirin Resistance (ARU ≥ 550) | The number of patients with aspirin reaction units (ARUs) values ≥ 550 on the Ultra Rapid Platelet Function Assay-ASA among the recruited patients | 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aspirin Resistance (ARU ≥ 500) | The number of participants with ARUs values ≥500 on the Ultra Rapid Platelet Function Assay-ASA; ARUs values | 4 weeks after reatment | 
| Bleeding Time (BT) | for evaluation of the extent of the bleeding time prolongation by additional cilostazol | 4 weeks after reatment | 
| Fatal or Major Bleeding Complications; | Fatal or life-threatening 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 | events ocurred during study medication after randomization | 
| Any Bleeding Complications | any bleeding events causing medical attention | events ocurred during study medication after randomization | 
| Difference of Post-treatment ARU and Baseline ARU | summation of change of ARU (posttreatment ARU - baseline ARU) of individual patients | baseline ARU measured at the randomization and post-treatment ARU measured at the 4weeks treatment with study medication | 
| Post-treatment ARU | mean of ARU value of individual participants after 4 weeks treatment | after 4 weeks treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infarction, Cerebral, Cilostazol, Aspirin Resistance