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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00050817
• Other study ID #: EFC4505
• Status: Completed
• Phase: Phase 3
• First received: December 20, 2002
• Last updated: April 20, 2012
• Start date: October 2002
• Est. completion date: August 2005

Study information

• Verified date: April 2012
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15603
• Est. completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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

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

Intervention

Drug:
• clopidogrel (SR25990)

Locations

Country	Name	City	State
Argentina	Sanofi-aventis Administrative Office	Buenos Aires
Australia	Sanofi-aventis Administrative Office	Macquarie Park
Austria	Sanofi-aventis Administrative Office	Wien
Belgium	Sanofi-aventis Administrative Office	Diegem
Brazil	Sanofi-aventis Administrative Office	Sao Paulo
Canada	Sanofi-aventis Administrative Office	Laval
Chile	Sanofi-aventis Administrative Office	Santiago
Czech Republic	Sanofi-aventis Administrative Office	Praha
Denmark	Sanofi-aventis Administrative Office	Horsholm
Finland	Sanofi-aventis Administrative Office	Helsinki
France	Sanofi-aventis Administrative Office	Paris
Germany	Sanofi-aventis Administrative Office	Berlin
Greece	Sanofi-aventis Administrative Office	Athens
Hong Kong	Sanofi-aventis Administrative Office	Causeway Bay
Hungary	Sanofi-aventis Administrative Office	Budapest
Italy	Sanofi-aventis Administrative Office	Milano
Malaysia	Sanofi-aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-aventis Administrative Office	Mexico
Netherlands	Sanofi-aventis Administrative Office	Gouda
Norway	Sanofi-aventis Administrative Office	Lysaker
Poland	Sanofi-aventis Administrative Office	Warszawa
Portugal	Sanofi-aventis Administrative Office	Porto Salvo
Russian Federation	Sanofi-aventis Administrative Office	Moscow
Singapore	Sanofi-aventis Administrative Office	Singapore
South Africa	Sanofi-aventis Administrative Office	Midrand
Spain	Sanofi-aventis Administrative Office	Barcelona
Sweden	Sanofi-aventis Administrative Office	Bromma
Switzerland	Sanofi-aventis Administrative Office	Geneva
Taiwan	Sanofi-aventis Administrative Office	Taipei
Turkey	Sanofi-aventis Administrative Office	Istanbul
United Kingdom	Sanofi-aventis Administrative Office	Guildford Surrey
United States	The Cleveland Clinic Foundation	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (2)

Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Rib — View Citation

Bhatt DL, Paré G, Eikelboom JW, Simonsen KL, Emison ES, Fox KA, Steg PG, Montalescot G, Bhakta N, Hacke W, Flather MD, Mak KH, Cacoub P, Creager MA, Berger PB, Steinhubl SR, Murugesan G, Mehta SR, Kottke-Marchant K, Lincoff AM, Topol EJ; CHARISMA Investig — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of myocardial infarction,stroke or cardiovascular death.
Secondary	severe bleeding