Cilostazol-Aspirin Therapy Against Recurrent Stroke With Intracranial Artery Stenosis

Cilostazol-Aspirin Therapy Against Recurrent Stroke With Intracranial Artery Stenosis (CATHARSIS)

Multi-center, open-labelled randomized controlled trial, to study the effect of aspirin plus cilostazol and aspirin alone on the progression of intracranial arterial stenosis, in 200 chronic stroke patients with 50-99% stenosis, to be followed up for 2 years

Study Overview

• Status: Completed
• Conditions: Cerebrovascular Disease
• Intervention / Treatment: Drug: Asprin, Cilostazol

Detailed Description

Intracraial arterial stenosis (IAS) is more common in Asia, including Japanese, than in Cocasian. Also, stroke recurrence rate is high in patients with such lesions, despite medical treatment. Accoding to the result of WASID (N Engl J Med 2005;352:1305-16), warfarin is not recommended because of the concern of safety (higher risk of intracranial hemorrhage and death when compared with aspirin), wheras the efficacy of aspirin is not enough in symptomatic IAS patients. Under these conditions, we planned to conduct a nationwide multi-center, open labelled, randomized controlled trial to compare the effect of aspirin plus cilostazol (phosphodiestrase type 3 inhibitor) and aspirin alone on the progression of IAS in 200 IAS patients with ischemic stroke after 2 weeks to 6 months of onset. Patients are randomly allocated to either of two groups. Aspirin 100mg/day plus cilostazol 200 mg/day is given to the 100 patients in one group, and aspirin 100 mg/day alone is given to 100 patients in another group.

Follow-up period is at least two years. The primary endpoint is progression of IAS on MRA at two years after randomization. The secondary endpoints are cardiovascular events (ischemic stroke, myocardial infarct, and other vascular events), death, serious adverse events, new silent brain infarcts, and activity of daily life. The purpose of this study is to establish the best medical treatment in symptomatic IAS patients. This study will also provide important information for the future randomized controlled study to compare medical treatment alone and intravascular intervetnion (PTA and/or stenting) in these patients.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Ischemic stroke after two weeks to six months from onset,
• (2) Responsible lesion identified on MRI,
• ( 3) Intracranial arterial stenosis >50% on MRA in the territory of responsible lesion,
• (4) Intracranial arterial stenosis in suproclinoid internal carotid arterry, M1 portion of midlle cerebral artery, or basilar artery,
• (5) Age of 45 to 85 years,
• (6) Able to visit out-patient clinic, and
• (7) Written informed consent obtained from patient or family.

Exclusion Criteria:

• (1) Patients with potential cardiac embolic sources,
• (2) Patients receiving cilostazol,
• (3) Patients on warfarin treatment,
• (4) Patients in whom MRI cannot be perfomed,
• (5) Patients in whom PTA or bypass surgery is planned,
• (6) Patients with history of symptomatic intracranial hemorrhage, other hemorrhagic diseases (active peptic ulcer etc.), hemophilia or coagulation abnormalities,
• (7) Patients with hypersensitivity to cilostazol or aspirin,
• (8) Patients with congestive heart failure or uncontrollable angina pectoris,
• (9) Patients with thrombocytopenia (<100,000/mm3),
• (10) Patients with liver dysfunction (AST or ALT >100 IU/L),
• (11) Patients with renal dysfunction (Creatinin >2.0 mg/dl),
• (12) Patients who cannot to be followed up during the study period,
• (13) Patients who are enrolled in other clinical trials, and
• (14) Patients inadequate for this study by other reasons.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression of intracranial arterial stenosis after two years

Secondary Outcome Measures

Outcome Measure
Cardiovascular events (ischemic stroke, cardiac infarctin, and other vascular events ）,
death (stroke death, vascular death except for stroke ）,
serious adverse events, new silent brain infarcts, and degrees of activity of daily living.

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: China National Center for Cardiovascular Diseases; Kyushu University; Tohoku University; Foundation for Biomedical Research and Innovation; Kobe City General Hospital; Neurology, Tokyo Women's Medical University, School of Medicine; Department of Neurology, Saiseikai Central Hospital
• Investigators: Principal Investigator: Shinichiro Uchiyama, M.D. PhD, Department of Neurology, Tokyo Women's Medical University School of Medicine; Principal Investigator: Nobuyuki Sakai, M.D. PhD, Kobe City General Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 1, 2006
• First Submitted That Met QC Criteria: June 1, 2006
• First Posted (Estimate): June 2, 2006

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: cilostazol; Clinical trials; Drug therapy, combination; intracranial arteriosclerosis; Platelete aggrigation inhibitors dual antiplatelet therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebrovascular Disorders; 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: UHA STROKE04-01