Resistance to Aspirin and/or Clopidogrel Among Patients With PAD.

Condition(s) targeted: Intermittent Claudication

Intervention: Clopidogrel (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Aalborg Hospital

Official(s) and/or principal investigator(s):
Nils Johannesen, MD, Principal Investigator, Affiliation: Department of Vascular Surgery, Aalborg Hospital

Overall contact:
Esben H Madsen, MD, Phone: +01-604 221 1536, Email: ehmadsen@gmail.com

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 receive 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.

Official title: Prevalence of Resistance to Aspirin and/or Clopidogrel Among Patients With PAD. Prognostic Significance of Resistance to Aspirin

Study design: Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Primary outcome:

Myocardial infarction

Unstable angina

Cerebral infarction

Transitory cerebral ischaemia

Percutaneous or surgical vascular intervention

Sudden deterioration of symptoms

Amputation

Death

Detailed description: 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, percutaneous or surgical vascular intervention, amputation, death.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): 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 contraception (intrauterine 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 surgical procedures performed within the last 3 month

- Severe renal disease

- Severe hepatic disease

- Breast feeding

- Pregnancy

Esben H Madsen, MD, Phone: +01-604 221 1536, Email: ehmadsen@gmail.com

Department of Vascular Surgery, Aalborg Hospital, Aalborg 9000, Denmark; Recruiting
Nils Johannesen, MD
Norbert Gehr, MD
Nils Johannesen, MD, Principal Investigator

Starting date: January 2006
Last updated: September 27, 2006