Clinical trial NCT01248351: Reversibility of Dual Antiplatelet Therapy by Platelets
Official title: Reversibility of Dual Antiplatelet Therapy by Platelets.Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bleeding
Keywords: aspirin, clopidogrel, pharmacodynamics, platelet transfusion
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: CSL Behring
First posted: 2010-11-25
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamic assessment of platelet function as assessed by 5 and 20 micromolar ADP
timeFrame: 7 days
Secondary outcomes:
measure: Pharmacodynamic assessment of platelet function as assessed by 20 mM arachidonic acid
timeFrame: 7 days
measure: Pharmacodynamic assessment of platelet function as assessed by Vasodilator stimulated phosphoprotein (VASP) phosphorylation (platelet reactivity index; PRI)
timeFrame: 7 days
measure: Pharmacodynamic assessment of platelet function as assessed by expression of GP IIb/IIIa receptors and P-selectin (Mean fluorescence intensity %)
timeFrame: 7 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of anesthesia and intensive care medicine, Medical Univerity of Graz
Study officials:
affiliation: Dept. of Anesthesia and Intensive Care Medicine, Medical University of Graz
name: Mahla Elisabeth, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pruller F, Drexler C, Archan S, Macher S, Raggam RB, Mahla E. Low platelet reactivity is recovered by transfusion of stored platelets: a healthy volunteer in vivo study. J Thromb Haemost. 2011 Aug;9(8):1670-3. doi: 10.1111/j.1538-7836.2011.04392.x. No abstract available.