Carotid Artery Stenting With Cilostazol Addition for Restenosis (CAS-CARE)

Effect of Cilostazol on In-stent Restenosis After Carotid Artery Stenting; Multi-center, Prospective, Randomized, Open-label Blind-endpoint Trial

CAS-CARE study was conducted to evaluate the inhibitory effect of cilostazol, compared to that of other antiplatelet drugs, on in-stent restenosis following carotid artery stenting (CAS) in patients scheduled to undergo CAS. Study design is Multicenter Prospective Ranodomized Controlled Study, rondomized by cilostazol/non-cilostazol group prior to CAS. 900 patients will be enrolled for 2 years and followed 2 years with in-stent restenosis after CAS, evaluated by carotid ultrasound and angiography.

Study Overview

• Status: Completed
• Conditions: In-stent Restenosis After Carotid Artery Stenting
• Intervention / Treatment: Drug: Cilostazol or Non-Cilostazol

Detailed Description

Restenosis after carotid artery stenting (CAS) is a critical issue. Cilostazol can reduce restenosis after interventions in coronary or femoropopliteal arteries. The investigators confirmed and published periprocedural cilostazol administration reduced incidences of in-stent restenosis (ISR) or target vessel revascularization (TVR) after CAS, retrospectively.

CAS-CARE study is Multicenter Prospective Ranodomized Controlled Study. Patients, scheduled for CAS within 30 days, 50% or more symptomatic carotid stenosis or 80% or more asymptomatic carotid stenosis, will enroll and randomize by cilostazol/non-cilostazol group. 900 patients will be enrolled for 2 years and followed 2 years with in-stent restenosis after CAS, evaluated by carotid ultrasound and angiography. And, evaluate cardiovascular events, including stroke, myocardial infarction, and hemorrhagic events in periprocedural period and followed period. In this study, ISR is diagnosed by ultrasound and DSA/CTA. Equivalence of CTA to ultrasound will be studied.

• Study Type: Interventional
• Enrollment (Actual): 707
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0046
      • Kobe City Medical Center General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 50% or more symptomatic carotid artery stenosis or 80% or more asymptomatic carotid artery stenosis
• scheduled for carotid artery stenting within 30 days
• 45 or more years-old and less than 80 years old
• antiplatelet agents can be administratered orally
• follow-up is anticipated possible for 2 years after CAS
• self-supporoted in daily activities (modified Rankin Scale 2 or less)
• patients who have given informed consent to participation in the study

Exclusion Criteria:

• received endovascular interevention
• scheduled for bilateral carotid intervention
• aortitis or cvasculitis
• congessive heart failure
• ischemic stroke within 48 hours
• hemorrhagic stroke within 90 days
• renal failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilostazol group; Continuous administration of cilostazol (unrestricted use of other antiplatelet agents and concomitant drugs)	Drug: Cilostazol or Non-Cilostazol; Cilostazol group administrate 100-200mg/day per oral, unrestricted use of other antiplatelet agents and concomitant drugs.; Other Names: Cilostazol (Pretal) group; Non-Cilostazol (Pretal) group
Active Comparator: Non-Cilostazol group; Antiplatelet agent other than cilostazol (unrestricted use of concomitant drugs)	Drug: Cilostazol or Non-Cilostazol; Cilostazol group administrate 100-200mg/day per oral, unrestricted use of other antiplatelet agents and concomitant drugs.; Other Names: Cilostazol (Pretal) group; Non-Cilostazol (Pretal) group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of in-stent restenosis within 2 years after CAS and time to occurrence	Difinition of endpoint is 50% or more in-stent restenosis detected by carotid ultrasound or angiopraphy. In cases restenosis does not occur, the final observation point will be used as the final evaluation point.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular event, death, hemorrhagic event, in-stent restenosis, new out-stent stenosis, or retreatment of stented artery within 2 yrs	Any events, including death, cardiovascular event(stroke, myocardial infarction), hemorrhagic event, in-stent restenosis, new out-stent stenosis, retreatment of stented artery, within 2 years	2 years
In-stent restenosis, new out-stent stenosis, or retreatment within 2 years	In-stent restenosis, new out-stent stenosis detected by ultrasound or CTA/DSA, or retreatment of stented artery within 2 years	2 years
hemorrhagic event within 2 years	hemorrhagic stroke, major hemorrhage required 2 unit or more transfusion	2 years
stroke within 2 years	any ischemic or hemorrhagic stroke	2 years
In-stent restenosis, new out-stent stenosis, or retreatment of stented artery, cardiovascular event, or death from any cause within 30 days	Any peri-procedural events; in-stent restenosis, new out-stent stenosis, or retreatment of stented artery, cardiovascular event(stroke, myocardial infarction), or death from any cause	30 days
Severe in-stent restenosis within 2 yrs	70% or more in-stent restenosis, diagnosed by ultrasound or DSA/CTA,	2 yeras
Change from baseline in max-IMT in both common carotid arteries	Intima-Media thickness of common carotid artery measured by ultrasound	2 years

Collaborators and Investigators

• Sponsor: Kobe City General Hospital
• Collaborators: Osaka University; Okayama University; Kobe University; Nagoya University; Kyoto University; Mie University; Wakayama Medical University; Nagasaki University; Yamaguchi University Hospital; Chiba University; Foundation for Biomedical Research and Innovation; Fukuoka University
• Investigators: Principal Investigator: Hiroshi Yamagami, MD, PhD, Kobe City Medical Center General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: December 11, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimate): December 16, 2010

Study Record Updates

• Last Update Posted (Actual): October 16, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Carotid Artery Stenting; Carotid Artery Disease; In stent restenosis; Cardiovascular event; Intima Media Thickness
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: TRIBRAIN1010; UMIN000004705 (Other Identifier: University hospital Medical Information Network, Japan)