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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00050817




Registration number
NCT00050817
Ethics application status
Date submitted
20/12/2002
Date registered
23/12/2002
Date last updated
23/04/2012

Titles & IDs
Public title
Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA)
Scientific 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.
Secondary ID [1] 0 0
EFC4505
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arteriosclerosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of myocardial infarction,stroke or cardiovascular death.
Timepoint [1] 0 0
Secondary outcome [1] 0 0
severe bleeding
Timepoint [1] 0 0

Eligibility
Key inclusion 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
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2002
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2005
Sample size
Target
Accrual to date
Final
15603
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-aventis Administrative Office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Ohio
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Belgium
State/province [4] 0 0
Diegem
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Canada
State/province [6] 0 0
Laval
Country [7] 0 0
Chile
State/province [7] 0 0
Santiago
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha
Country [9] 0 0
Denmark
State/province [9] 0 0
Horsholm
Country [10] 0 0
Finland
State/province [10] 0 0
Helsinki
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Greece
State/province [13] 0 0
Athens
Country [14] 0 0
Hong Kong
State/province [14] 0 0
Causeway Bay
Country [15] 0 0
Hungary
State/province [15] 0 0
Budapest
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Malaysia
State/province [17] 0 0
Kuala Lumpur
Country [18] 0 0
Mexico
State/province [18] 0 0
Mexico
Country [19] 0 0
Netherlands
State/province [19] 0 0
Gouda
Country [20] 0 0
Norway
State/province [20] 0 0
Lysaker
Country [21] 0 0
Poland
State/province [21] 0 0
Warszawa
Country [22] 0 0
Portugal
State/province [22] 0 0
Porto Salvo
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Moscow
Country [24] 0 0
Singapore
State/province [24] 0 0
Singapore
Country [25] 0 0
South Africa
State/province [25] 0 0
Midrand
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Sweden
State/province [27] 0 0
Bromma
Country [28] 0 0
Switzerland
State/province [28] 0 0
Geneva
Country [29] 0 0
Taiwan
State/province [29] 0 0
Taipei
Country [30] 0 0
Turkey
State/province [30] 0 0
Istanbul
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT00050817
Trial related presentations / publications
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-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-17. doi: 10.1056/NEJMoa060989. Epub 2006 Mar 12.
Bhatt DL, Pare 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 Investigators. The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study. Eur Heart J. 2012 Sep;33(17):2143-50. doi: 10.1093/eurheartj/ehs059. Epub 2012 Mar 26.
Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.
Bangalore S, Bhatt DL, Steg PG, Weber MA, Boden WE, Hamm CW, Montalescot G, Hsu A, Fox KA, Lincoff AM. beta-blockers and cardiovascular events in patients with and without myocardial infarction: post hoc analysis from the CHARISMA trial. Circ Cardiovasc Qual Outcomes. 2014 Nov;7(6):872-81. doi: 10.1161/CIRCOUTCOMES.114.001073. Epub 2014 Sep 30.
Berger PB, Bhatt DL, Fuster V, Steg PG, Fox KA, Shao M, Brennan DM, Hacke W, Montalescot G, Steinhubl SR, Topol EJ; CHARISMA Investigators. 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. Circulation. 2010 Jun 15;121(23):2575-83. doi: 10.1161/CIRCULATIONAHA.109.895342. Epub 2010 Jun 1.
Steinhubl SR, Bhatt DL, Brennan DM, Montalescot G, Hankey GJ, Eikelboom JW, Berger PB, Topol EJ; CHARISMA Investigators. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med. 2009 Mar 17;150(6):379-86. doi: 10.7326/0003-4819-150-6-200903170-00006.
Mak KH, Bhatt DL, Shao M, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Montalescot G, Steg PG, Steinhubl SR, Fox KA, Topol EJ. The influence of body mass index on mortality and bleeding among patients with or at high-risk of atherothrombotic disease. Eur Heart J. 2009 Apr;30(7):857-65. doi: 10.1093/eurheartj/ehp037. Epub 2009 Feb 20.
Eikelboom JW, Hankey GJ, Thom J, Bhatt DL, Steg PG, Montalescot G, Johnston SC, Steinhubl SR, Mak KH, Easton JD, Hamm C, Hu T, Fox KA, Topol EJ; Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) Investigators. Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk. Circulation. 2008 Oct 21;118(17):1705-12. doi: 10.1161/CIRCULATIONAHA.108.768283. Epub 2008 Oct 6.
Bhatt DL, Flather MD, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Fabry-Ribaudo L, Hu T, Topol EJ, Fox KA; CHARISMA Investigators. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007 May 15;49(19):1982-8. doi: 10.1016/j.jacc.2007.03.025. Epub 2007 Apr 11.
Public notes

Contacts
Principal investigator
Name 0 0
ICD CSD
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00050817