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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00050817
First received: December 20, 2002
Last updated: April 20, 2012
Last verified: April 2012
  Purpose

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.

Condition Intervention Phase
Arteriosclerosis
Drug: clopidogrel (SR25990)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Occurrence of myocardial infarction,stroke or cardiovascular death.

Secondary Outcome Measures:
  • severe bleeding

Enrollment: 15603
Study Start Date: October 2002
Study Completion Date: August 2005
Detailed 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.
  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00050817

  Show 32 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: ICD CSD Sanofi
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: ICD Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00050817     History of Changes
Other Study ID Numbers: EFC4505
Study First Received: December 20, 2002
Last Updated: April 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Embolism

Additional relevant MeSH terms:
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Clopidogrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014