Physiopathology of Rapid Aspirin Desensitization

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01118546

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hypersensitivity Coronary Artery Disease

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.

Study Design

Study Type:

Observational

Actual Enrollment :

86 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Physiopathology of Rapid Aspirin Desensitization in Patients With Coronary Artery Disease and a History of Hypersensitivity to Aspirin or NSAIDs

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
controls 2 patient without CAD, not on aspirin and without history of hypersensitivity
case of hypersensitivity patient with CAD on aspirin, with a history of hypersensitivity
controls 1 patient with CAD on aspirin, without history of hypersensitivity

Outcome Measures

Primary Outcome Measures

Platelet aggregation in response to arachidonic acid Basophil activation tests Platelet aggregation in response to arachidonic acid Basophil activation tests [day 1, after aspirin desensitization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

Age > 18 years
Admitted to Hospital BICHAT, in Cardiology
Patients with aspirin or NSAID intolerance due to hypersensitivity
Imperative cardiological indications for aspirin, such as acute coronary syndrome, or placement of a stent
Written informed consent
Patient with health insurance coverage

EXCLUSION CRITERIA:

Ongoing ST elevation acute coronary syndrome
Ongoing signs or symptoms of hypersensitivity or allergy (asthma, urticaria, Quincke' edema, or other allergic symptoms)