Official Title: “PACT (Platelet Activity After Clopidogrel Termination)”

Clopidogrel is a medication that is used to decrease the ability of platelets to form blood clots.

The theory has been proposed that, in patients with coronary artery disease or stroke, increased platelet function after discontinuation of clopidogrel therapy is associated with an increased clotting risk. However, this theory has never been rigorously tested.

The goal of this research is to determine whether discontinuation of clopidogrel results in increased platelet function.

Study Type: Interventional

Study Design: Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacodynamics Study

Study Primary Completion Date: July 2009

In this study, we will address the question: does discontinuation of clopidogrel result in platelet hyperreactivity? We will perform a double-blind, placebo-controlled, crossover study in normal subjects, in whom platelet reactivity will be measured before clopidogrel or placebo, during clopidogrel or placebo, and at various time points after discontinuation of clopidogrel or placebo. The dose of clopidogrel will be the standard, FDA-approved dose: 75 mg daily. All subjects will be treated with aspirin 81 mg daily throughout the 57 days of study assessment in both the clopidogrel arm and the placebo arm, because the clinically relevant question is: in patients who remain on aspirin, does discontinuation of clopidogrel result in platelet hyperreactivity?

Intervention(s) in this Clinical Trial

• Drug: clopidogrel + aspirin
  • The subject will be randomized to either clopidogrel 75 mg plus aspirin 81 mg or to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel or placebo) will then be discontinued and aspirin continued for another 43 days. After a period of 0 - 30 days of no study drug and no aspirin, the subject will be crossed-over to either clopidogrel 75 mg plus aspirin 81 mg or to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel or placebo) will then be discontinued and aspirin continued for another 43 days. Blood sampling will be drawn at 8 timepoints during each arm of the study for a total of 16 blood samples.
• Drug: placebo + aspirin
  • The subject will be randomized to either clopidogrel 75 mg plus aspirin 81 mg or to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel or placebo) will then be discontinued and aspirin continued for another 43 days. After a period of 0 - 30 days of no study drug and no aspirin, the subject will be crossed-over to either clopidogrel 75 mg plus aspirin 81 mg or to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel or placebo) will then be discontinued and aspirin continued for another 43 days. Blood sampling will be drawn at 8 timepoints during each arm of the study for a total of 16 blood samples.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • The subjects will be randomized to clopidogrel 75 mg plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., clopidogrel) will then be discontinued and aspirin continued for another 43 days.
• Placebo Comparator: 2
  • The subjects will be randomized to placebo plus aspirin 81 mg orally daily for 14 days. The study drug (i.e., placebo) will then be discontinued and aspirin continued for another 43 days.

Primary Measures

• Platelet reactivity will be measured by low-dose ADP-induced platelet surface activated GPIIb-IIIa complex, as reported by monoclonal antibody PAC1 in a whole blood flow cytometric assay.
  • Time Frame: The assay will be measured on blood drawn from subjects at 8 timepoints during each arm of the study (clopidogrel and placebo)
    Safety Issue?: No

Secondary Measures

• ADP, TRAP and collagen induced platelet surface activated GPIIb-IIIa, platelet surface P-selectin, and platelet aggregation. Soluble CD40L, P-selectin, and other plasma markers.
  • Time Frame: All assays will be performed on blood drawn from subjects at 8 timepoints during each arm of the study (clopidogrel and placebo)
    Safety Issue?: No

Inclusion Criteria:

• Must be a normal healthy subject
• Must be between 21-70 years old
• Must be able to take aspirin and clopidogrel.
• Must be able to have blood drawn 16 times over approximately 3 months.

Exclusion Criteria:

• Subject who is currently taking aspirin or another anti-platelet drug such as clopidogrel. Subject must be free of these medications for 10 days before enrolling in this study.
• Subject who is currently taking a non-steroidal anti-inflammatory drug such as ibuprofen or naproxen. Subject must be free of these medications for 3 days before enrolling in this study.
• Subject who is currently taking medications for depression or medications that lower blood pressure or lower blood sugar.
• Subject who are pregnant or may become pregnant during the study or who is breast feeding.
• Subject with a known allergy to aspirin or clopidogrel.
• Cigarette smoking or use of other nicotine product.
• Subject with a history of any of the following: coronary artery disease; stroke;
• bleeding disorder; ongoing bleeding; previous life-threatening hemorrhage; stomach ulcers; gastrointestinal bleeding within the past 1 month; major surgery within the past 1 month; minor surgery within the past 2 weeks; or platelet transfusion within the past 7 days.
• Subject with a blood count, measured on the pre-study drug blood sample, that is not in the normal range.
• Subject who is enrolled in another clinical trial of an investigational drug.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Massachusetts

Overall Clinical Trial Officials and Contacts

Alan D. Michelson, M.D. Principal Investigator University of Massachusetts Medical School  

Overall Contact: Marsha L Fox, MS, RN 508-856-0059 fox@platelets.org

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00619073

Study ID Number: CPFS 2008-1

ClinicalTrials.gov Identifier: NCT00619073

Health Authority: United States: Institutional Review Board

Home page of the study principal investigator