Clinical trial NCT01995370: Cilostazol Stroke Prevention Study for Antiplatelet Combination
Official title: Cilostazol Stroke Prevention Study for Antiplatelet Combination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Noncardioembolic Cerebral Infarction
Keywords: Noncardioembolic cerebral infarction
Dual antiplatelet therapy (DAPT)
Cilostazol
Aspirin
Clopidogrel
Lead sponsor: Japan Cardiovascular Research Foundation
Sponsor class: OTHER
Collaborators: name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2013-11-26
Enrollment: 1884
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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


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:

  1. at least 50% stenosis of a major intracranial artery (to the level of A2, M2, or P2)
  2. at least 50% stenosis of an extracranial artery (the common carotid artery，internal carotid artery，vertebral artery，brachiocephalic artery，or subclavian artery)
  3. 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

Primary outcomes:
measure: Recurrence of symptomatic ischemic stroke, with the symptoms lasting for at least 24 hours
timeFrame: every 6 months
Secondary outcomes:
measure: Any stroke [ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)]
timeFrame: every 6 months
measure: SAH or ICH
timeFrame: every 6 months
measure: IS or transient ischemic attack (TIA)
timeFrame: every 6 months
measure: Death from any cause
timeFrame: every 6 months
measure: Stroke (IS，ICH，SAH), myocardial infarction (MI), or vascular death
timeFrame: every 6 months
measure: All vascular events: stroke, MI, and other vascular events
timeFrame: every 6 months
measure: Adverse events and adverse drug reactions
timeFrame: every 6 months
measure: Severe or life-threatening hemorrhage (GUSTO Criteria)
timeFrame: every 6 months
Other outcomes:
Locations:
city: Osaka
country: Japan
facility: Japan Cardiovascular Research Foundation
Study officials:
affiliation: National Cerebral and Cardiovascular Center, Japan
name: Takenori Yamaguchi, President emeritus
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.