Reversibility of Dual Antiplatelet Therapy by Platelets

Medical University of Graz

Status and phase: Completed; Phase 2

Conditions: Bleeding

Treatments: Other: administration of autologous stored platelets; Biological: autologous stored platelets

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01248351

2009-018108-17 (EudraCT Number)

PAC_2009

Details and patient eligibility

About

The objective of the study is to test the hypothesis whether or not autologous stored platelets are able to offset the antiplatelet effect of aspirin and clopidogrel as assessed by state-of-the-art platelet function assays.

Full description

Dual antiplatelet therapy with aspirin and clopidogrel is a well established strategy to prevent thrombotic complications in patients with high platelet reactivity following plaque rupture in acute coronary syndromes (ACS) or percutaneous coronary interventions. Current practice guidelines for antiplatelet therapy advocate a one to 12 months dual antiplatelet therapy after bare metal stent PCI and a 12 months dual antiplatelet therapy after PCI in patients with ACS and drug eluting stent PCI. Although oral antiplatelet therapy is associated with both, short- as well as long-term clinical efficacy, irreversible platelet inhibition carries a substantial risk of bleeding particularly in patients presenting for surgery. Empiric therapy of bleeding consists of platelet transfusion. However, there are currently no pharmacodynamic studies assessing the effect of stored platelets on in-vitro platelet function tests.

Healthy volunteers will donate platelets, take aspirin and clopidogrel for 3 days (loading dose aspirin 300 mg, clopidogrel 300 mg, maintenance dose aspirin 100 mg, clopidogrel 75 mg) and platelets will be retransfused on the 4th day. Pharmacodynamic measurements of platelet function will be performed at baseline, after drug intake before retransfusion, immediately after retransfusion and 24 hours thereafter.

Enrollment: 6 patients

Sex: All

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Informed consent
2. Healthy volunteers, male or female (after exclusion of pregnancy if they are on birth control pill or have a contraceptive coil implanted)
3. Age of consent
4. Weight: 70 kg - 100 kg
5. Platelet count 240 000 to 440 000/µL
6. Hematocrit > 40%
7. readiness to refrain from any activities prone to injury during the study period.

Exclusion criteria

1. Allergy against aspirin or clopidogrel
2. History of bleeding
3. History of peptic ulcer
4. Intake of aspirin or NSAR during the last ten days before screening
5. Gastrointestinal disease precluding resorption of aspirin and clopidogrel
6. Scheduled surgery
7. Any current medication
8. History of hepatic disease
9. 20µm ADP induced aggregation < 60% at screening
10. CYP2C19 polymorphisms
11. Donation of blood within the preceding 4 weeks
12. Neurotic disease
13. Current smoking
14. Drug addiction
15. Intake of grapefruits during the last 10 days before

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

autologous stored platelets

Experimental group

Treatment:

Biological: autologous stored platelets

Other: administration of autologous stored platelets

Biological: autologous stored platelets