Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA)

Arteriosclerosis Clinical Trial

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.

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arteriosclerosis

• NCT number: NCT00050817
• Study type: Interventional
• Source: Sanofi
• Status: Completed
• Phase: Phase 3
• Start date: October 2002
• Completion date: August 2005