Post-marketing Study of Cilostazol (Cilostazol Stroke Prevention Study 2)

Post-marketing Study of Cilostazol: Study to Confirm Efficacy in Preventing Recurrent Cerebral Infarction in Comparison With Aspirin

The purpose of this study is to investigate the efficacy of cilostazol in preventing recurrence of cerebral infarction and the safety of long-term administration of the drug (100 mg, twice daily) in patients with cerebral infarction (excluding cardiogenic cerebral embolism) in a multi-center, double-blind, parallel-group comparison with aspirin (81 mg, once daily).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 2800
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Otsuka Pharmaceutical Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with stable medical conditions for 182 days (26 weeks) after occurrence of cerebral infarction
2. Patients in whom the infarct-related foci was detected by X-ray CT scan or MRI
3. Patients aged 20 to 80 years (inclusive) at time of consent
4. Patients with none of the following cardiac diseases that may be associated with cardiogenic cerebral embolism: mitral stenosis, prosthetic heart valve, endocarditis, myocardial infarction within 6 weeks after occurrence, ventricular aneurysm, endocardial thrombosis, mitral valve prolapse (patients less than 45 years of age in whom no other cause was identified), atrial fibrillation, sick sinus syndrome, idiopathic cardiomyopathy, and patent foramen ovale
5. Patients without asymptomatic cerebral infarction
6. Patients who have neither undergone nor are scheduled to undergo percutaneous transluminal angioplasty or revascularization for the treatment of cerebral infarction
7. Patients without severe disturbances/impairments following occurrence of cerebral

Exclusion Criteria:

1. Patients with hemorrhage or bleeding tendency (hemophilia, capillary fragility, intracranial hemorrhage, hemorrhage in the digestive tract, hemorrhage in the urinary tract, hemoptysis, and hemorrhage in the vitreous body)
2. Pregnant, possibly pregnant, or nursing women
3. Patients with ischemic heart failure
4. Patients with peptic ulcer
5. Patients with severer blood disorders
6. Patients with severe hepatic or renal
7. Patients with malignant neoplasm or patients who have received any therapy for malignant neoplasm within 5 years prior to entering the study
8. Patients with a history of hypersensitivity to salicylic acid formulations or ingredients of cilostazol tablets
9. Patients with aspirin asthma (asthma attacks induced by nonsteroidal antiinflammatory analgesic agents) or a history of aspirin asthma
10. Patients who are being treated with ticlopidine hydrochloride
11. Patients who are participating in another study for an investigational drug
12. Patients who are otherwise judged inappropriate for inclusion in the study by the investigators

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; cilostazol	Drug: Cilostazol; oral tablet, 100 mg twice a day and placebo of aspirin once a day, 1 to 5years
Active Comparator: 2; Aspirin	Drug: Aspirin; oral tablet, placebo of cilostazol twice a day and 81 mg once a day, 1 to 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of Patients With First Occurence of Stroke	The endpoint in this measure is a composite endpoint of the first recurrence of cerebral infarction, or occurrence of cerebral haemorrhage or subarachnoid haemorrhage. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.	From start of treatment to end of follow-up period ( follow-up periods : 29 months [Standard Deviation 16, range 1-59 months])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With First Recurrence of Cerebral Infarction		From start of treatment to end of follow-up period (mean follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months])
Number of Patients With First Occurrence of Ischaemic Cerebrovascular Disease	The endpoint in this measure is a composite endpoint of the first recurrence of cerebral infarction or the first occurrence of transient ischaemic attack. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.	From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months])
Number of Deaths From Any Cause	Number of deaths from any cause. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.	From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months])
Number of Patients With First Occurrence of a Composite Endpoint of Stroke, Haemorrhagic Events, or Cardiovascular Events	The endpoint in this measure is a composite endpoint of the first recurrence of cerebral infarction, or occurrence of cerebral haemorrhage, subarachnoid haemorrhage, transient ischaemic attack, angina pectris, myocardial infarction, heart failure, or haemorrhage requiring hospital admission. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.	From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months])

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With First Occurrence of Haemorrhagic Event	The endpoint in this measure is a composite endpoint of the first occurrence of cerebral haemorrhage, subarachnoid haemorrhage or haemorrhage requiring hospital admission. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.	From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months])

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Masahiko Abe, Division of New Product Evaluation and Development

Publications and helpful links

General Publications

• Shinohara Y, Katayama Y, Uchiyama S, Yamaguchi T, Handa S, Matsuoka K, Ohashi Y, Tanahashi N, Yamamoto H, Genka C, Kitagawa Y, Kusuoka H, Nishimaru K, Tsushima M, Koretsune Y, Sawada T, Hamada C; CSPS 2 group. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol. 2010 Oct;9(10):959-68. doi: 10.1016/S1474-4422(10)70198-8. Epub 2010 Sep 15.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: October 4, 2005
• First Submitted That Met QC Criteria: October 4, 2005
• First Posted (Estimate): October 6, 2005

Study Record Updates

• Last Update Posted (Estimate): June 10, 2011
• Last Update Submitted That Met QC Criteria: June 9, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• 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; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Aspirin; Cilostazol
• Other Study ID Numbers: C02100-002; JapicCTI-050034; UMIN-CTR-C000000129