1000 patients with atherosclerosis of lower limbs are examined to evaluate the activity of the platelets during the standard treatment, including aspirin. A minor group will recieve clopidogrel instead of aspirin for 2 weeks.

The main hypothesis is that high platelet activity at the beginning of the study is associated with a higher risk of atherothrombosis. Follow up time is 6 years.

Condition	Intervention	Phase
Intermittent Claudication	Drug: Clopidogrel	Phase IV

Further study details as provided by Aalborg Hospital:

Primary Outcomes: Myocardial infarction; Unstable angina; Cerebral infarction; Transitory cerebral ischaemia; Percutaneous or sugical vascular intervention; Sudden deterioration of symptoms; Amputation; Death
Expected Total Enrollment:  1000

Patients with atherosclerosis of the lower limbs are at high risk of atherothrombosis, mainly heart attack and stroke. The medical treatment of these patients include platelet inhibiting drugs, usually aspirin, to reduce the risk of blood clot formation. Clopidogrel is another platelet inhibiting drug, which is prescribed less often, primarily because of the high costs compared to aspirin.

Phenomena of ''''resistance'''' to these drugs have been described by numerous investigators. Essentially resistance means that the effect of the drug described is less than expected or missing, when described by various laboratory methods. We still do not know which way resistance is best described, and we still do not know if patients who are ''''resistant'''' to either drug are less protected against future heart attacks or strokes.

Main objectives:

• To measure the activity of platelets in these patients during aspirin treatment.
• To measure the activity of platelets in a minor population of these patients during clopidogrel treatment.
• To evaluate the prognostic significance of resistance to aspirin in these patients.

Secondary objectives:

- To describe the relation between drug resistance and the level of inflammatory markers in the blood.

Methods:

Platelet activity is measured by the PFA-100 (Dade Behring) and by traditional turbidimetric aggregation.

Patients:

Number needed is 1000.

Follow up:

6 years

Endpoints:

Myocardial infarction, unstable angina, cerebral infarction, transitory cerebral ischaemia, sudden deterioration of symptoms, percutaneus or surgical vascular intervention, amputation, death.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Atherosclerosis of the lower limbs, defined by one of the following criteria: Ancle-Brachial Pressure Index (ABPI)< 0.9, intermittent claudication, ischaemic pain at rest, ischaemic ulcers or gangrene.
• Age > 18 years
• For fertile women: Use of safe contraseption (intra-uterine contraceptive device, the pill, hormonal skin patches, progestogen injections, progestogen implant, vaginal ring)

Exclusion Criteria:

• Allergy to either Aspirin or Clopidogrel
• Known bleeding disorder
• Platelet count < 140 mia/L or > 400 mia/L
• Intake of NSAID''''s, SSRI''''s or Dipyridamol within the preceding 14 days
• Not radically treated gastrointestinal ulceration within the last 6 month
• Greater sugical procedures performed within the last 3 month
• Severe renal disease
• Severe hepatic disease
• Breast feeding
• Pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00262561

Esben Hjorth Madsen, MD      +01-604 221 1536    ehmadsen@gmail.com
Norbert Gehr, MD      +45-99 32 29 79    aas.u30030@nja.dk

Study chairs or principal investigators

Nils Johannesen, MD,  Principal Investigator,  Department of Vascular Surgery, Aalborg Hospital   

Study ID Numbers:  2005-003844-68
Last Updated:  December 8, 2005
Record first received:  December 6, 2005
ClinicalTrials.gov Identifier:  NCT00262561
Health Authority: Denmark: Danish Medicines Agency; Denmark: The Danish National Committee on Biomedical Research Ethics
ClinicalTrials.gov processed this record on 2006-01-10