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Physiopathology of Rapid Aspirin Desensitization

Completed
Conditions
Hypersensitivity
Coronary Artery Disease
Registration Number
NCT01118546
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

Aspirin is very effective in protecting patients with coronary artery disease against adverse cardiac events, because it is a potent "antiplatelet agent". Some patients may develop a history of hypersensitivity to aspirin and treatment cannot usually be resumed in these patients. We have developed a rapid procedure to induce tolerance in these patients (SILBERMAN et al, Am J CARDIOL 2005;95:509-10) and wish to test whether aspirin is as effective as antiplatelet agent in patients with a history of allergy to aspirin and who undergo desensitization as it is in patients without history of hypersensitivity

Detailed Description

Previous studies in allergology have proved the safety of desensitization procedures in allergic patients with an imperative indication for a medication. This tolerance state is usually obtained after a cumbersome procedure requiring several hours to days. We have adapted successfully such a procedure to the patients with acute coronary artery disease requiring urgent aspirin (excluding the ST elevation myocardial infarction) (SILBERMAN et al, Am J CARDIOL 2005;95:509-10).

Patients with a history of Aspirin or NonSteroidal Anti-Inflammatory Drugs hypersensitivity appear to have alterations of eicosanoid metabolism : these drugs trigger an imbalance toward the leucotriene pathway. This case-control study aims to

* evaluate after desensitization therapy the anti-aggregant effect of aspirin in these very particular patients : clinical outcome, PFA test, levels of the urinary metabolite of thromboxane A2 (11 dehydro thromboxane B2) and also usual aggregation tests.

* assess the in VITRO basophil activation induced by aspirin before and after desensitization procedure by flow cytometric cellular allergen test using basophils surface marker and mediators' dosage. Before the challenge procedure these tests aim to confirm the clinically established diagnosis of hypersensitivity. After desensitization, these tests intend to better assess the efficiency of the induced tolerance, to attempt to identify predictors of successful desensitization as well as identify potential cross reactivity with other NSAIDs..

This procedure is indicated in all patients with aspirin or NSAID intolerance with imperative cardiological indications for aspirin, such as acute coronary syndrome, or placement of a stent. The desensitization procedure must be performed in a coronary care unit; the patients are duly informed about benefits and risks of the challenge and provide written informed consent. Desensitization consists in rapidly escalating aspirin dose administration with ad hoc aspirin capsules prepared by the hospital pharmacist. Blood and urinary samples are obtained during the hospital stay for coronary and desensitization care. An additional blood and urine sample will be obtained 6 to 8 weeks later during an outpatient visit in the laboratory. Initial biological data will be compared to those of two control groups matched for age, gender and type of acute coronary syndrome :

* Controls 1: patients with CAD on aspirin, without history of hypersensitivity

* Controls 2: patients without CAD, not on aspirin and without history of hypersensitivity.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
86
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Platelet aggregation in response to arachidonic acid Basophil activation tests Platelet aggregation in response to arachidonic acid Basophil activation testsday 1, after aspirin desensitization
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Centre hospitalier Bichat Claude Bernard

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Paris,, France

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