Official Title: “A Phase III, Multicenter, Multinational, Randomized, Parallel Group, Double-Blind Trial of Clopidogrel Versus Placebo in High-Risk Patients Aged 45 Years and Older, at Risk of Atherothrombotic Events, and Who Are Receiving Background Therapy Including Low-Dose ASA.”

RATIONALE: - Atherothrombosis is a progressive and generalized vascular disease resulting in events leading to myocardial infarction (heart attack), stroke, and vascular death. - In patients at risk for this disease, it is characterized by an unpredictable, sudden disruption of atherosclerotic plaques, which may lead to total occlusion of artery due to formation of a clot. The use of aspirin (blood thinner agent) for reducing those major ischemic events is either indicated, or recommended by international guidelines.

However, aspirin fails to prevent a high percentage of such life-threatening events.

Therefore, more effective blood thinning therapy may provide additional clinical benefit to such patients. - The results of the CURE trial in patients with unstable angina demonstrate the additional benefit of long-term treatment (up to one year) with clopidogrel, (a blood thinner agent), when administered in combination with standard therapy including aspirin. The purpose of CHARISMA is to investigate whether a similar clinical benefit of clopidogrel may apply to a broad population of high-risk patients receiving low-dose aspirin therapy. Such population includes patients with previous cardiovascular, neurovascular or peripheral arterial manifestations of atherothrombosis and patients with combinations of recognized risk factors for atherosclerosis.

OBJECTIVES: - To assess the efficacy of clopidogrel 75 mg once-daily by comparison with a placebo, in preventing cardiovascular morbidity/mortality. The study will compare the efficacy of the two regimens in preventing the occurrence of major cardiovascular complications (stroke, heart attack, cardiovascular death) in high-risk patients who are otherwise receiving low-dose aspirin therapy (75-162 mg daily). - To evaluate the safety of clopidogrel in this population, and more specifically the incidence of fatal or severe bleeding (as per GUSTO definition), in order to estimate the global benefit of clopidogrel in this patient population.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

TREATMENTS: - Clopidogrel (Plavix® and/or Iscover®) is an agent inhibiting platelet aggregation involved in clot formation. Each tablet contains 75mg of clopidogrel. A matching placebo of clopidogrel is an inactive substance that looks similar to the active clopidogrel tablet.

TREATMENT PLAN: - There will be two treatment groups; one will receive clopidogrel 75 mg (1 tablet qd), the second matching placebo of clopidogrel (1 tablet qd). These study drugs will be administered on top of low-dose aspirin (75-162 mg qd) systematically prescribed to such patients. In addition, patients enrolled in CHARISMA will be managed as appropriate for their risk factors for atherosclerosis: eg. high blood pressure, high cholesterol, diabetes…etc.

PRIMARY ENDPOINT: - Combined endpoint of cardiovascular mortality, stroke, acute myocardial infarction.

STUDY EXECUTION: - Some 7,600 patients per group will be recruited within two years. Patients will be observed over a maximum of 3.5 years.

STUDY TERRITORY: - Approximately 900 sites throughout North/South America, Europe, Asia, Australia, and South Africa.

Intervention(s) in this Clinical Trial

• Drug: Clopidogrel

Primary Measures

• Occurrence of myocardial infarction,stroke or cardiovascular death.

Secondary Measures

• severe bleeding

INCLUSION:

• Be at least 45 years old and comply with at least one of the four categories of inclusion criteria:
• Combination of atherothrombotic risk factors (2 major or 3 minor or 1 major + 2 minor risk factors among those listed below)
• Major atherothrombotic risk factors
• Type I or II diabetes (under drug therapy)
• Diabetic nephropathy
• Ankle brachial index (ABI) < 0.9
• Asymptomatic carotid stenosis >= 70%
• At least one carotid plaque as evidenced by intima-media thickness (IMT)
• Minor atherothrombotic risk factors
• Systolic blood pressure (SBP) >= 150 mmHg, despite appropriate therapy for at least 3 months
• Primary hypercholesterolemia
• Current smoking > 15 cigarettes per day
• Male >= 65 years
• Female >= 70 years
• and/or
• Documented cerebrovascular disease (TIA or IS within 5 years) and/or
• Documented coronary artery disease (stable angina with documented multivessel coronary disease, previous documented MI, multivessel PCI or CABG within 1 year, multivessel
• CABG older than 1 year associated with current angina) and/or
• Documented symptomatic PAD

EXCLUSION:

• Absolute indication for the use of clopidogrel, high-dose aspirin (>162 mg), NSAIDs, or oral anti-thrombotic drugs
• Absolute contraindication to the use of clopidogrel or aspirin
• Clinical conditions likely to interfere with follow-up leading to inability to complete the trial

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

ICD CSD Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00050817

Study ID Number: EFC4505

ClinicalTrials.gov Identifier: NCT00050817

Health Authority: United States: Food and Drug Administration