Back to resultsCilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS・com)
Primary Purpose
Noncardioembolic Cerebral Infarction
Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
aspirin
clopidogrel
cilostazol
Sponsored by
About this trial
This is an interventional prevention trial for Noncardioembolic Cerebral Infarction focused on measuring Noncardioembolic cerebral infarction, Dual antiplatelet therapy (DAPT), Cilostazol, Aspirin, Clopidogrel
Eligibility Criteria
Inclusion Criteria:
- Patients with a diagnosis of noncardioembolic IS that developed between 8 and 180 days before the start of the protocol treatment
- Patients with a responsible lesion identified by MRI
- Patients aged 20 to 85 years old when providing informed consent
- Patients taking clopidogrel or aspirin alone as antiplatelet therapy when providing informed consent
Patients meeting at least one of the following criteria a-c:
- at least 50% stenosis of a major intracranial artery (to the level of A2, M2, or P2)
- at least 50% stenosis of an extracranial artery (the common carotid artery，internal carotid artery，vertebral artery，brachiocephalic artery，or subclavian artery)
Two or more of the following risk factors
- Aged 65 years or more
- Diabetes mellitus
- Hypertension
- Peripheral arterial disease
- Chronic kidney disease
- History of IS (excluding the index IS for this study)
- History of ischemic heart disease
- Smoking (only current smokers)
- Patients considered to be able to visit the study site for ambulatory care throughout the observation period
- Patients who provided written informed consent
Exclusion Criteria:
- Patients with emboligenic heart disease
- Patients taking any anticoagulant agents
- Patients who cannot undergo MRI examination for reasons such as claustrophobia and implanted pacemaker
- Patients scheduled to undergo any surgery, such as percutaneous angioplasty, stent placement, and bypass grafting, during the study period
- Patients with a drug-eluting coronary stent implanted within one year
- Patients with a history of symptomatic non-traumatic intracranial hemorrhage, any other hemorrhagic disease (eg, active peptic ulcer), bleeding predisposition, or blood clotting disorders
- Patients with a history of hypersensitivity to cilostazol
- Patients with congestive heart failure or uncontrolled angina pectoris
- Patients with thrombocytopenia (platelet count ≦ 100,000/mm3)
- Patients with severe liver or renal dysfunction
- Women who are pregnant, breast-feeding, or of child-bearing potential
- Patients with a malignant tumor requiring treatment
Patients who are taking aspirin, and meet any of the following criteria:
- History of hypersensitivity to aspirin or salicylic acid analogues
- Current peptic ulcer
- Aspirin-induced asthma or its history
Patients who are taking clopidogrel, and meet the following criterion:
・History of hypersensitivity to clopidogrel
- Patients who are participating in any other clinical studies
- Patients considered by the investigator/subinvestigator to be unsuitable for participating in this study
Sites / Locations
- Japan Cardiovascular Research Foundation
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Monotherapy group
DAPT group
Arm Description
Aspirin (81mg or 100mg) or clopidogrel (50mg or 75mg) will be orally administered once daily. The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Cilostazol (100mg twice daily) will be orally administered in combination with aspirin (81 or 100mg once daily) or clopidogrel (50 or 75mg once daily). The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Outcomes
Primary Outcome Measures
Recurrence of symptomatic ischemic stroke, with the symptoms lasting for at least 24 hours
An "ischemic stroke" hereafter indicates a symptomatic ischemic stroke.
Secondary Outcome Measures
Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)]
SAH or ICH
IS or transient ischemic attack (TIA)
Death from any cause
Stroke (IS，ICH，SAH), myocardial infarction (MI), or vascular death
All vascular events: stroke, MI, and other vascular events
Adverse events and adverse drug reactions
Severe or life-threatening hemorrhage (GUSTO Criteria)
Full Information
NCT ID
NCT01995370
First Posted
November 15, 2013
Last Updated
March 26, 2019
Sponsor
Japan Cardiovascular Research Foundation
Collaborators
Otsuka Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01995370
Brief Title
Cilostazol Stroke Prevention Study for Antiplatelet Combination
Acronym
CSPS・com
Official Title
Cilostazol Stroke Prevention Study for Antiplatelet Combination
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
December 13, 2013 (Actual)
Primary Completion Date
December 7, 2018 (Actual)
Study Completion Date
December 7, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Japan Cardiovascular Research Foundation
Collaborators
Otsuka Pharmaceutical Co., Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To examine the efficacy and safety of dual antiplatelet therapy (DAPT) including cilostazol (Pletaal OD Tablet ®) in comparison with antiplatelet monotherapy (excluding cilostazol) for secondary prevention of ischemic stroke in high-risk patients for stroke
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Noncardioembolic Cerebral Infarction
Keywords
Noncardioembolic cerebral infarction, Dual antiplatelet therapy (DAPT), Cilostazol, Aspirin, Clopidogrel
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1884 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Monotherapy group
Arm Type
Active Comparator
Arm Description
Aspirin (81mg or 100mg) or clopidogrel (50mg or 75mg) will be orally administered once daily.
The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Arm Title
DAPT group
Arm Type
Experimental
Arm Description
Cilostazol (100mg twice daily) will be orally administered in combination with aspirin (81 or 100mg once daily) or clopidogrel (50 or 75mg once daily).
The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Intervention Type
Drug
Intervention Name(s)
aspirin
Other Intervention Name(s)
Bayaspirin
Intervention Description
Aspirin (81mg or 100mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Intervention Type
Drug
Intervention Name(s)
clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
Clopidogrel (50mg or 75mg) will be orally administered once daily.The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Intervention Type
Drug
Intervention Name(s)
cilostazol
Other Intervention Name(s)
Pletaal OD Tablet
Intervention Description
Cilostazol (100mg twice daily) will be orally administered. The treatment period will begin with the first visit of the first subject and end one year after the first visit of the last subject.
Primary Outcome Measure Information:
Title
Recurrence of symptomatic ischemic stroke, with the symptoms lasting for at least 24 hours
Description
An "ischemic stroke" hereafter indicates a symptomatic ischemic stroke.
Time Frame
every 6 months
Secondary Outcome Measure Information:
Title
Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)]
Time Frame
every 6 months
Title
SAH or ICH
Time Frame
every 6 months
Title
IS or transient ischemic attack (TIA)
Time Frame
every 6 months
Title
Death from any cause
Time Frame
every 6 months
Title
Stroke (IS，ICH，SAH), myocardial infarction (MI), or vascular death
Time Frame
every 6 months
Title
All vascular events: stroke, MI, and other vascular events
Time Frame
every 6 months
Title
Adverse events and adverse drug reactions
Time Frame
every 6 months
Title
Severe or life-threatening hemorrhage (GUSTO Criteria)
Time Frame
every 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with a diagnosis of noncardioembolic IS that developed between 8 and 180 days before the start of the protocol treatment
Patients with a responsible lesion identified by MRI
Patients aged 20 to 85 years old when providing informed consent
Patients taking clopidogrel or aspirin alone as antiplatelet therapy when providing informed consent
Patients meeting at least one of the following criteria a-c:
at least 50% stenosis of a major intracranial artery (to the level of A2, M2, or P2)
at least 50% stenosis of an extracranial artery (the common carotid artery，internal carotid artery，vertebral artery，brachiocephalic artery，or subclavian artery)
Two or more of the following risk factors
Aged 65 years or more
Diabetes mellitus
Hypertension
Peripheral arterial disease
Chronic kidney disease
History of IS (excluding the index IS for this study)
History of ischemic heart disease
Smoking (only current smokers)
Patients considered to be able to visit the study site for ambulatory care throughout the observation period
Patients who provided written informed consent
Exclusion Criteria:
Patients with emboligenic heart disease
Patients taking any anticoagulant agents
Patients who cannot undergo MRI examination for reasons such as claustrophobia and implanted pacemaker
Patients scheduled to undergo any surgery, such as percutaneous angioplasty, stent placement, and bypass grafting, during the study period
Patients with a drug-eluting coronary stent implanted within one year
Patients with a history of symptomatic non-traumatic intracranial hemorrhage, any other hemorrhagic disease (eg, active peptic ulcer), bleeding predisposition, or blood clotting disorders
Patients with a history of hypersensitivity to cilostazol
Patients with congestive heart failure or uncontrolled angina pectoris
Patients with thrombocytopenia (platelet count ≦ 100,000/mm3)
Patients with severe liver or renal dysfunction
Women who are pregnant, breast-feeding, or of child-bearing potential
Patients with a malignant tumor requiring treatment
Patients who are taking aspirin, and meet any of the following criteria:
History of hypersensitivity to aspirin or salicylic acid analogues
Current peptic ulcer
Aspirin-induced asthma or its history
Patients who are taking clopidogrel, and meet the following criterion:
・History of hypersensitivity to clopidogrel
Patients who are participating in any other clinical studies
Patients considered by the investigator/subinvestigator to be unsuitable for participating in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takenori Yamaguchi, President emeritus
Organizational Affiliation
National Cerebral and Cardiovascular Center, Japan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Japan Cardiovascular Research Foundation
City
Osaka
ZIP/Postal Code
565-8565
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35074890
Citation
Toyoda K, Omae K, Hoshino H, Uchiyama S, Kimura K, Miwa K, Minematsu K, Yamaguchi K, Suda Y, Toru S, Kitagawa K, Ihara M, Koga M, Yamaguchi T; CSPS.com Trial Investigators. Association of Timing for Starting Dual Antiplatelet Treatment With Cilostazol and Recurrent Stroke: A CSPS.com Trial Post Hoc Analysis. Neurology. 2022 Mar 8;98(10):e983-e992. doi: 10.1212/WNL.0000000000200064. Epub 2022 Jan 24.
Results Reference
derived
PubMed Identifier
34622679
Citation
Uchiyama S, Toyoda K, Omae K, Saita R, Kimura K, Hoshino H, Sakai N, Okada Y, Tanaka K, Origasa H, Naritomi H, Houkin K, Yamaguchi K, Isobe M, Minematsu K, Matsumoto M, Tominaga T, Tomimoto H, Terayama Y, Yasuda S, Yamaguchi T. Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis. J Am Heart Assoc. 2021 Oct 19;10(20):e022575. doi: 10.1161/JAHA.121.022575. Epub 2021 Oct 8.
Results Reference
derived
PubMed Identifier
34404237
Citation
Hoshino H, Toyoda K, Omae K, Ishida N, Uchiyama S, Kimura K, Sakai N, Okada Y, Tanaka K, Origasa H, Naritomi H, Houkin K, Yamaguchi K, Isobe M, Minematsu K, Matsumoto M, Tominaga T, Tomimoto H, Terayama Y, Yasuda S, Yamaguchi T; CSPS.com Trial Investigators. Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial. Stroke. 2021 Nov;52(11):3430-3439. doi: 10.1161/STROKEAHA.121.034378. Epub 2021 Aug 18.
Results Reference
derived
PubMed Identifier
31122494
Citation
Toyoda K, Uchiyama S, Yamaguchi T, Easton JD, Kimura K, Hoshino H, Sakai N, Okada Y, Tanaka K, Origasa H, Naritomi H, Houkin K, Yamaguchi K, Isobe M, Minematsu K; CSPS.com Trial Investigators. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2019 Jun;18(6):539-548. doi: 10.1016/S1474-4422(19)30148-6.
Results Reference
derived
PubMed Identifier
25487817
Citation
Toyoda K, Uchiyama S, Hoshino H, Kimura K, Origasa H, Naritomi H, Minematsu K, Yamaguchi T; CSPS.com Study Investigators. Protocol for Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com): a randomized, open-label, parallel-group trial. Int J Stroke. 2015 Feb;10(2):253-8. doi: 10.1111/ijs.12420. Epub 2014 Dec 8.
Results Reference
derived
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Cilostazol Stroke Prevention Study for Antiplatelet Combination
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