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

• ClinicalTrials.gov Identifier: NCT00234065
• Recruitment Status: Completed
• First Posted: October 6, 2005
• Results First Posted: May 13, 2011
• Last Update Posted: June 10, 2011
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by: Otsuka Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Cerebral Infarction	Drug: Cilostazol; Drug: Aspirin	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Post-marketing Study of Cilostazol: Study to Confirm Efficacy in Preventing Recurrent Cerebral Infarction in Comparison With Aspirin
• Study Start Date: December 2003
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Numbers of Patients With First Occurence of Stroke [ Time Frame: From start of treatment to end of follow-up period ( follow-up periods : 29 months [Standard Deviation 16, range 1-59 months]) ]
   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.

Secondary Outcome Measures :

1. Number of Patients With First Recurrence of Cerebral Infarction [ Time Frame: From start of treatment to end of follow-up period (mean follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months]) ]
2. Number of Patients With First Occurrence of Ischaemic Cerebrovascular Disease [ Time Frame: From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months]) ]
   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.
3. Number of Deaths From Any Cause [ Time Frame: 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. The evaluation committee, whose members were unaware of patients' treatment assignment, adjudicated all trial endpoints.
4. Number of Patients With First Occurrence of a Composite Endpoint of Stroke, Haemorrhagic Events, or Cardiovascular Events [ Time Frame: From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months]) ]
   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.

Other Outcome Measures:

1. Number of Patients With First Occurrence of Haemorrhagic Event [ Time Frame: From start of treatment to end of follow-up period ( follow-up periods : 29 months [STANDARD DEVIATION 16, range 1-59 months]) ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Japan

Otsuka Pharmaceutical Co., Ltd.

Tokyo, Japan

Sponsors and Collaborators

Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Masahiko Abe; Division of New Product Evaluation and Development

More Information

Publications of Results:

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.

• Responsible Party: Katsuhisa Saito, OPCJ
• ClinicalTrials.gov Identifier: NCT00234065
• Other Study ID Numbers: C02100-002; JapicCTI-050034; UMIN-CTR-C000000129
• First Posted: October 6, 2005
• Results First Posted: May 13, 2011
• Last Update Posted: June 10, 2011
• Last Verified: June 2011

Additional relevant MeSH terms:

Cerebral Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Vascular Diseases; Cardiovascular Diseases; Aspirin; Cilostazol; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors