Overcome Biochemical Aspirin Resistance Through Cilostazol Combination (ARCC)

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebral Infarction
• Intervention / Treatment: Drug: Cilostazol; Drug: placebo

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

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Jae-Kwan Cha
  • Daejon, Korea, Republic of, 302-799
    • Eulji University Hospital
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 134-701
    • Kangdong Sacred Heart Hospital, Hallym University

Participation Criteria

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Cilostazol; 100mg of Cilostazol twice a day	Drug: Cilostazol; cilostazol 100mg twice a day for 4 weeks; Other Names: pletaal
Placebo Comparator: Placebo; matching placebo to cilostazol	Drug: placebo; placebo 1 tablet twice a day matching for cilostazol; 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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Korea Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Sun U Kwon, MD. PhD., Asan Medical Center, Univsersity of Ulsan, Medical College

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 12, 2007
• First Submitted That Met QC Criteria: March 12, 2007
• First Posted (Estimate): March 13, 2007

Study Record Updates

• Last Update Posted (Estimate): January 18, 2010
• Last Update Submitted That Met QC Criteria: December 10, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: Infarction, Cerebral; Cilostazol; Aspirin Resistance
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Brain Infarction; Infarction; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: ARCC