NCT00050817

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.

Completed Phase 3 Last updated 20 April 2012

What this trial tests

Phase 3 trial testing clopidogrel (SR25990) in Arteriosclerosis in 15,603 participants. Completed in 1 August 2005.

Timeline

1 October 2002

1 August 2005

Quick facts

Lead sponsor	Sanofi
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	15,603
Start date	1 October 2002
Estimated completion	1 August 2005
Sites	32 locations across United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile

Drugs / interventions tested

• clopidogrel (SR25990) — full drug profile →

Conditions studied

• Arteriosclerosis — all drugs for Arteriosclerosis →

Sponsor

Sanofi — full company profile →

Who can join

45 and older, any sex, with Arteriosclerosis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Occurrence of myocardial infarction,stroke or cardiovascular death.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.
   Bhatt DL, Fox KA, Hacke W, Berger PB, et al · · 2006 · cited 1704× · PMID 16531616 · DOI 10.1056/nejmoa060989
2. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
   Bhatt DL, Flather MD, Hacke W, Berger PB, et al · · 2007 · cited 516× · PMID 17498584 · DOI 10.1016/j.jacc.2007.03.025
3. Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.
   Berger PB, Bhatt DL, Fuster V, Steg PG, et al · · 2010 · cited 169× · PMID 20516378 · DOI 10.1161/circulationaha.109.895342
4. β-blockers and cardiovascular events in patients with and without myocardial infarction: post hoc analysis from the CHARISMA trial.
   Bangalore S, Bhatt DL, Steg PG, Weber MA, et al · · 2014 · cited 75× · PMID 25271049 · DOI 10.1161/circoutcomes.114.001073
5. The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study.
   Bhatt DL, Paré G, Eikelboom JW, Simonsen KL, et al · · 2012 · cited 68× · PMID 22450429 · DOI 10.1093/eurheartj/ehs059
6. Cardiovascular Pharmacogenomics: Does It Matter If You're Black or White?
   De T, Park CS, Perera MA. · · 2019 · cited 23× · PMID 30296897 · DOI 10.1146/annurev-pharmtox-010818-021154
7. Long-term outcomes in high-risk patients with non-ST-segment elevation myocardial infarction.
   Cohen M. · · 2016 · cited 17× · PMID 26001907 · DOI 10.1007/s11239-015-1227-1
8. Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis.
   De Carlo M, Di Minno G, Sayre T, Fazeli MS, et al · · 2021 · cited 16× · PMID 32819249 · DOI 10.2174/1570161118666200820141131