PACT (Platelet Activity After Clopidogrel Termination) - Full Text View

Sponsor:	University of Massachusetts
Collaborators:	Sanofi-Aventis Bristol-Myers Squibb
Information provided by:	University of Massachusetts
ClinicalTrials.gov Identifier:	NCT00619073

Purpose

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.

Condition	Intervention
Blood Platelets Clopidogrel	Drug: clopidogrel + aspirin Drug: placebo + aspirin

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	PACT (Platelet Activity After Clopidogrel Termination)

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners

Drug Information available for: Acetylsalicylic acid Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by University of Massachusetts:

Primary Outcome 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) ] [ Designated as safety issue: No ]

Secondary Outcome 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) ] [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	April 2008
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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.	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.
2: Placebo Comparator 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.	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

Assigned Interventions

1: Active Comparator

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.

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.

2: Placebo Comparator

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.

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.

Detailed Description:

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?

Eligibility

Ages Eligible for Study:	21 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619073

Contacts

Contact: Marsha L Fox, MS, RN

508-856-0059

fox@platelets.org

Locations

United States, Massachusetts
University of Massachusetts Medical School	Recruiting
Worcester, Massachusetts, United States, 01655-0002
Contact: Marsha L. Fox, MS, RN 508-856-0059 fox@platelets.org
Principal Investigator: Alan D. Michelson, M.D.
Sub-Investigator: Andrew L. Frelinger, Ph.D.

Sponsors and Collaborators

University of Massachusetts

Sanofi-Aventis

Bristol-Myers Squibb

Investigators

Principal Investigator:

Alan D. Michelson, M.D.

University of Massachusetts Medical School

More Information

Additional Information:

Home page of the study principal investigator This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Massachusetts Medical School ( Alan D. Michelson, M.D., Director, Center for Platelet Function Studies )
Study ID Numbers:	CPFS 2008-1
Study First Received:	February 6, 2008
Last Updated:	February 20, 2009
ClinicalTrials.gov Identifier:	NCT00619073 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Massachusetts:

blood platelets
platelet aggregation inhibitors
antiplatelet drugs
clopidogrel

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
Aspirin

Analgesics, Non-Narcotic
Sensory System Agents
Clopidogrel
Therapeutic Uses
Platelet Aggregation Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010