Reversibility of Dual Antiplatelet Therapy by Platelets

Bleeding Clinical Trial

Official title:

Reversibility of Dual Antiplatelet Therapy by Platelets.Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01248351
• Other study ID #: PAC_2009
• Secondary ID: 2009-018108-17
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2010
• Last updated: April 27, 2011
• Start date: November 2010
• Est. completion date: March 2011

Study information

• Verified date: April 2011
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 30 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bleeding

Intervention

Other:
• autologous stored platelets
Administration of autologous stored platelets
• administration of autologous stored platelets
administration of autologous stored platelets

Biological:
• autologous stored platelets
transfusion of autologous stored platelets

Locations

Country	Name	City	State
Austria	Department of anesthesia and intensive care medicine, Medical Univerity of Graz	Graz

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Graz	CSL Behring, Novo Nordisk A/S

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamic assessment of platelet function as assessed by 5 and 20 micromolar ADP	pharmacodynamic measurements of platelet function will be assessed at baseline, after 3 days administration of aspirin and clopidogrel (300 mg loading with aspirin and clopidogrel, maintenance with 100 mg aspirin and 75 mg clopidogrel, respectively) after retransfusion of stored platelets and 24 hours thereafter	7 days	Yes
Secondary	Pharmacodynamic assessment of platelet function as assessed by 20 mM arachidonic acid	pharmacodynamic measurements of platelet function will be assessed at baseline, after 3 days administration of aspirin and clopidogrel (300 mg loading with aspirin and clopidogrel, maintenance with 100 mg aspirin and 75 mg clopidogrel, respectively) after retransfusion of stored platelets and 24 hours thereafter	7 days	Yes
Secondary	Pharmacodynamic assessment of platelet function as assessed by Vasodilator stimulated phosphoprotein (VASP) phosphorylation (platelet reactivity index; PRI)	pharmacodynamic measurements of platelet function will be assessed at baseline, after 3 days administration of aspirin and clopidogrel (300 mg loading with aspirin and clopidogrel, maintenance with 100 mg aspirin and 75 mg clopidogrel, respectively) after retransfusion of stored platelets and 24 hours thereafter	7 days	Yes
Secondary	Pharmacodynamic assessment of platelet function as assessed by expression of GP IIb/IIIa receptors and P-selectin (Mean fluorescence intensity %)	pharmacodynamic measurements of platelet function will be assessed at baseline, after 3 days administration of aspirin and clopidogrel (300 mg loading with aspirin and clopidogrel, maintenance with 100 mg aspirin and 75 mg clopidogrel, respectively) after retransfusion of stored platelets and 24 hours thereafter	7 days	Yes