Reversibility of Dual Antiplatelet Therapy by Platelets

NCT ID: NCT01248351

Last Updated: 2011-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-03-31

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.

Conditions

Bleeding

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

autologous stored platelets

Group Type: EXPERIMENTAL

autologous stored platelets

Intervention Type: OTHER

Administration of autologous stored platelets

administration of autologous stored platelets

Intervention Type: OTHER

administration of autologous stored platelets

autologous stored platelets

Intervention Type: BIOLOGICAL

transfusion of autologous stored platelets

Interventions

autologous stored platelets

Administration of autologous stored platelets

Intervention Type: OTHER

administration of autologous stored platelets

administration of autologous stored platelets

Intervention Type: OTHER

autologous stored platelets

transfusion of autologous stored platelets

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

CSL Behring

INDUSTRY

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Medical University of Graz

Principal Investigators

Mahla Elisabeth, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Anesthesia and Intensive Care Medicine, Medical University of Graz

Locations

Department of anesthesia and intensive care medicine, Medical Univerity of Graz

Graz, , Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 21649849 (View on PubMed)

Other Identifiers

2009-018108-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PAC_2009

Identifier Type: -

Identifier Source: org_study_id