Reversibility of Dual Antiplatelet Therapy by Platelets

This study has been completed.
Sponsor:
Collaborators:
Novo Nordisk A/S
CSL Behring
Information provided by:
Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01248351
First received: November 19, 2010
Last updated: April 27, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Bleeding
Other: autologous stored platelets
Other: administration of autologous stored platelets
Biological: autologous stored platelets
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reversibility of Dual Antiplatelet Therapy by Platelets.Phase II Study

Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Pharmacodynamic assessment of platelet function as assessed by 5 and 20 micromolar ADP [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Pharmacodynamic assessment of platelet function as assessed by 20 mM arachidonic acid [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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

  • Pharmacodynamic assessment of platelet function as assessed by Vasodilator stimulated phosphoprotein (VASP) phosphorylation (platelet reactivity index; PRI) [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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

  • Pharmacodynamic assessment of platelet function as assessed by expression of GP IIb/IIIa receptors and P-selectin (Mean fluorescence intensity %) [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    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


Enrollment: 6
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: autologous stored platelets Other: autologous stored platelets
Administration of autologous stored platelets
Other: administration of autologous stored platelets
administration of autologous stored platelets
Biological: autologous stored platelets
transfusion of autologous stored platelets

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

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01248351

Locations
Austria
Department of anesthesia and intensive care medicine, Medical Univerity of Graz
Graz, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
Novo Nordisk A/S
CSL Behring
Investigators
Principal Investigator: Mahla Elisabeth, MD Dept. of Anesthesia and Intensive Care Medicine, Medical University of Graz
  More Information

No publications provided by Medical University of Graz

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Univ. Prof. Dr. Elisabeth Mahla, Medical University of Graz
ClinicalTrials.gov Identifier: NCT01248351     History of Changes
Other Study ID Numbers: PAC_2009, 2009-018108-17
Study First Received: November 19, 2010
Last Updated: April 27, 2011
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Graz:
aspirin, clopidogrel, pharmacodynamics, platelet transfusion

ClinicalTrials.gov processed this record on October 19, 2014