Cilostazol Stroke Prevention Study for Antiplatelet Combination

NCT01995370 | Completed Phase 4 DMC

• 2 other identifiers: 021-TADD-1300-1000012180
• Study Type: interventional
• Target: 1,884
• Locations: 1 country
• Sites: 1

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

Conditions

Noncardioembolic Cerebral Infarction

Keywords

Noncardioembolic cerebral infarction; Dual antiplatelet therapy (DAPT); Cilostazol; Aspirin; Clopidogrel

Outcome Measures

Primary Outcomes (1)

• Recurrence of symptomatic ischemic stroke, with the symptoms lasting for at least 24 hours

  An "ischemic stroke" hereafter indicates a symptomatic ischemic stroke.

  every 6 months

Secondary Outcomes (8)

• Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)]

  every 6 months

• SAH or ICH

  every 6 months

• IS or transient ischemic attack (TIA)

  every 6 months

• Death from any cause

  every 6 months

• Stroke (IS，ICH，SAH), myocardial infarction (MI), or vascular death

  every 6 months

Study Arms (2)

Monotherapy group

ACTIVE COMPARATOR

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.

Drug: aspirin; Drug: clopidogrel

DAPT group

EXPERIMENTAL

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.

Drug: aspirin; Drug: clopidogrel; Drug: cilostazol

Interventions

aspirin DRUG

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.

Also known as: Bayaspirin

DAPT group; Monotherapy group

clopidogrel DRUG

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.

Also known as: Plavix

DAPT group; Monotherapy group

cilostazol DRUG

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.

Also known as: Pletaal OD Tablet

DAPT group

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Japan Cardiovascular Research Foundation: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Japan Cardiovascular Research Foundation

Osaka, 565-8565, Japan

Location

Related Publications (8)

• Koge J, Toyoda K, Koga M, Fukuda-Doi M, Uchiyama S, Kimura K, Hoshino H, Yamaguchi K, Okada Y, Sakai N, Miwa K, Minematsu K, Yamaguchi T; CSPS.com Trial Investigators. Effect of renal function on dual antiplatelet therapy using cilostazol for stroke prevention: a CSPS.com trial post hoc analysis. J Neurol Sci. 2025 Oct 15;477:123661. doi: 10.1016/j.jns.2025.123661. Epub 2025 Aug 18.

  PMID: 40845415 DERIVED

• Nishiyama Y, Kimura K, Otsuka T, Toyoda K, Uchiyama S, Hoshino H, Sakai N, Okada Y, Origasa H, Naritomi H, Houkin K, Yamaguchi K, Minematsu K, Matsumoto M, Tominaga T, Tomimoto H, Terayama Y, Yasuda S, Yamaguchi T; CSPS.com Trial Investigators. Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial. Stroke. 2023 Mar;54(3):697-705. doi: 10.1161/STROKEAHA.122.039900. Epub 2023 Feb 3.

  PMID: 36734235 DERIVED

• Uchiyama S, Toyoda K, Okamura S, Omae K, Hoshino H, Kimura K, Kitagawa K, Minematsu K, Yamaguchi T. Dual antiplatelet therapy with cilostazol in stroke patients with extracranial arterial stenosis or without arterial stenosis: A subgroup analysis of the CSPS.com trial. Int J Stroke. 2023 Apr;18(4):426-432. doi: 10.1177/17474930221112343. Epub 2022 Jul 21.

  PMID: 35762581 DERIVED

• 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.

  PMID: 35074890 DERIVED

• 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.

  PMID: 34622679 DERIVED

• 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.

  PMID: 34404237 DERIVED

• 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.

  PMID: 31122494 DERIVED

• 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.

  PMID: 25487817 DERIVED

MeSH Terms

Interventions

Aspirin; Clopidogrel; Cilostazol

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tetrazoles; Azoles; Quinolines

Study Officials

• Takenori Yamaguchi, President emeritus

  National Cerebral and Cardiovascular Center, Japan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2013
• First Posted: November 26, 2013
• Study Start: December 13, 2013
• Primary Completion: December 7, 2018
• Study Completion: December 7, 2018
• Last Updated: March 28, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)