PACT (Platelet Activity After Clopidogrel Termination)

This study has been completed.
Sponsor:
Collaborators:
Sanofi
Bristol-Myers Squibb
Information provided by (Responsible Party):
Alan Michelson, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier:
NCT00619073
First received: February 6, 2008
Last updated: November 8, 2012
Last verified: November 2012
  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
Drug: Aspirin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: PACT (Platelet Activity After Clopidogrel Termination)

Resource links provided by NLM:


Further study details as provided by University of Massachusetts, Worcester:

Primary Outcome Measures:
  • Change From Baseline in Platelet Surface Activated GPIIb-IIIa Complex at 45 Days After Intervention. [ Time Frame: Baseline and 45 days after intervention ] [ Designated as safety issue: No ]
    Value at 45 days after intervention minus value at baseline in platelet surface activated GPIIb-IIIa complex using flow cytometry.The types and concentrations of agonists used in the flow cytometry assays reported here were: ADP 0.5, 1, and 20 µmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 µmol/L; and a combination of collagen 5 µg/mL and epinephrine 5 µmol/L. Mean Florescence Intensity (MFI) is used as unit of measure. MFI indicates relative degree of shift in fluorescence intensity of a population of platelets in arbitrary units.


Enrollment: 15
Study Start Date: April 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Clopidogrel + aspirin
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
Clopidogrel 75mg plus aspirin 81mg, tablet by mouth daily for 14 days.
Other Names:
  • Plavix
  • aspirin
Drug: Aspirin
Aspirin 81mg tablet by mouth continued daily alone for 43 days after day 14.
Other Name: aspirin
Placebo Comparator: Placebo + aspirin
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
Placebo plus aspirin 81 mg, tablet by mouth daily for 14 days.
Other Name: aspirin
Drug: Aspirin
Aspirin 81mg tablet by mouth continued daily alone for 43 days after day 14.
Other Name: aspirin

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
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: NCT00619073

Locations
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655-0002
Sponsors and Collaborators
University of Massachusetts, Worcester
Sanofi
Bristol-Myers Squibb
Investigators
Principal Investigator: Alan D. Michelson, M.D. University of Massachusetts, Worcester
  More Information

Additional Information:
Publications:
Responsible Party: Alan Michelson, Study Principle Investigator, University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT00619073     History of Changes
Other Study ID Numbers: CPFS 2008-1
Study First Received: February 6, 2008
Results First Received: January 10, 2012
Last Updated: November 8, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Massachusetts, Worcester:
blood platelets
platelet aggregation inhibitors
antiplatelet drugs
clopidogrel

Additional relevant MeSH terms:
Aspirin
Ticlopidine
Clopidogrel
Platelet Aggregation Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 16, 2014