Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00528411
Recruitment Status : Completed
First Posted : September 12, 2007
Results First Posted : January 11, 2012
Last Update Posted : January 13, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated how long it takes for Ticagrelor to begin working and how long it takes for it to stop working after the last dose of drug. Ticagrelor will be compared to clopidogrel, an established anti-platelet treatment for preventing blood clots, and placebo plus Aspirin.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Ticagrelor Tablets Drug: Clopidogrel (over encapsulated) capsule Drug: Aspirin Tablets Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre Randomised, Double-blind, Double-dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of Ticagrelor Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease (CAD)
Study Start Date : October 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 1
Aspirin + Placebo
Drug: Aspirin Tablets
Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.
Other Name: ASA

Active Comparator: 2
Aspirin + clopidogrel
Drug: Clopidogrel (over encapsulated) capsule
Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)
Other Names:
  • Plavix
  • Clopidogrel Bisulfate

Drug: Aspirin Tablets
Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.
Other Name: ASA

Experimental: 3
Aspirin + Ticagrelor
Drug: Ticagrelor Tablets
Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)

Drug: Aspirin Tablets
Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.
Other Name: ASA




Primary Outcome Measures :
  1. Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose [ Time Frame: At 2 hours after first dose of study drug ]
    IPA(%)=(PAb-PAt)/PAb*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  2. Slope of Extent IPA Offset Curve 4 to 72 Hours After Last Dose of Study Drug [ Time Frame: 4 to 72 Hours after last dose of study drug ]
    IPA(%)=(PAb-PAt)/PAb*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. The unit for the slope of IPA curve is percent/hour.


Secondary Outcome Measures :
  1. Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose [ Time Frame: 0.5 hours after first dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  2. Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose [ Time Frame: 1 hour after first dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  3. Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose [ Time Frame: 4 hours after first dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  4. Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose [ Time Frame: 8 hours after first dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  5. Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose [ Time Frame: 24 hours after first dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  6. Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose [ Time Frame: 0 hour before last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  7. Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose [ Time Frame: 2 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  8. Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose [ Time Frame: 4 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  9. Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose [ Time Frame: 8 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  10. Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose [ Time Frame: 24 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  11. Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose [ Time Frame: 48 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  12. Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose [ Time Frame: 72 hours after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  13. Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose [ Time Frame: 120 hours - Day 5 after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  14. Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose [ Time Frame: 168 hours - Day 7 after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference of baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  15. Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose [ Time Frame: 240 hours - Day 10 after last dose ]
    IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  16. Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline ]
    FEV1 is measured by Spirometry, the unit is Liter.

  17. Cardiopulmonary Parameters at Post 6-week Treatment: FEV1 [ Time Frame: 6-week post treatment ]
    FEV1 is measured by Spirometry, the unit is Liter.

  18. Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC) [ Time Frame: Baseline ]
    FVC is measured by Spirometry, the unit is Liter.

  19. Cardiopulmonary Parameters at Post 6-week Treatment: FVC [ Time Frame: 6-week post treatment ]
    FVC is measured by Spirometry, the unit is Liter.

  20. Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio) [ Time Frame: Baseline ]
    FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.

  21. Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio [ Time Frame: 6-week post treatment ]
    FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.

  22. Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75) [ Time Frame: Baseline ]
    FEF25-75 is measured by Spirometry, the unit is Liter/Second.

  23. Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75 [ Time Frame: 6-week post treatment ]
    FEF25-75 is measured by Spirometry, the unit is Liter/Second.

  24. Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC) [ Time Frame: Baseline ]
    FRC is measured by Body Box Plethysmography, the unit is Liter.

  25. Cardiopulmonary Parameters Post 6-week Treatment: FRC [ Time Frame: 6-week post treatment ]
    FRC is measured by Body Box Plethysmography, the unit is Liter.

  26. Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC) [ Time Frame: Baseline ]
    TLC is measured by Body Box Plethysmography, the unit is Liter.

  27. Cardiopulmonary Parameters Post 6-week Treatment: TLC [ Time Frame: 6-week post treatment ]
    TLC is measured by Body Box Plethysmography, the unit is Liter.

  28. Cardiopulmonary Parameters at Baseline: Residual Volume (RV) [ Time Frame: Baseline ]
    RV is measured by Body Box Plethysmography, the unit is Liter.

  29. Cardiopulmonary Parameters Post 6-week Treatment: RV [ Time Frame: 6-week post treatment ]
    RV is measured by Body Box Plethysmography, the unit is Liter.

  30. Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE) [ Time Frame: Baseline ]
    VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute

  31. Cardiopulmonary Parameters Post 6-week Treatment: VE [ Time Frame: 6-week post treatment ]
    VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute

  32. Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR) [ Time Frame: Baseline ]
    RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.

  33. Cardiopulmonary Parameters Post 6-week Treatment: RR [ Time Frame: 6-week post treatment ]
    RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.

  34. Cardiopulmonary Parameters at Baseline: Tidal Volume (VT) [ Time Frame: Baseline ]
    VT is measured by Body Box Plethysmography, the unit is Liter/Minute.

  35. Cardiopulmonary Parameters Post 6-week Treatment: VT [ Time Frame: 6-week post treatment ]
    VT is measured by Body Box Plethysmography, the unit is Liter/Minute.

  36. Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB) [ Time Frame: Baseline ]
    DLCOSB is measured by Body Box Plethysmography, the unit is Percent.

  37. Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB [ Time Frame: 6-week post treatment ]
    DLCOSB is measured by Body Box Plethysmography, the unit is Percent.

  38. Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF) [ Time Frame: Baseline ]
    EF is measured by Echocardiogram, the unit is Percent. The ejection fraction is defined by: (LV diastolic volume - LV systolic volume)/LV diastolic volume. The unit % is the percentage change of left ventricular diastolic versus systolic volume relative to the diastolic volume. LV is the left ventricle.

  39. Cardiopulmonary Parameters Post 6-week Treatment: EF [ Time Frame: 6-week post treatment ]
    EF is measured by Echocardiogram, the unit is Percent. The ejection fraction is defined by: (LV diastolic volume - LV systolic volume)/LV diastolic volume. The unit % is the percentage change of left ventricular diastolic versus systolic volume relative to the diastolic volume. LV is the left ventricle.

  40. Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline ]
    NT-proBNP is measured by clinical lab, the unit is pg/mL.

  41. Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP [ Time Frame: 6-week post treatment ]
    NT-proBNP is measured by clinical lab, the unit is pg/mL.

  42. Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2) [ Time Frame: Baseline ]
    SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.

  43. Cardiopulmonary Parameters Post 6-week Treatment: SpO2 [ Time Frame: 6-week post treatment ]
    SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented stable Coronary Artery Disease (stable angina, previous MI history, previous history of revascularization);
  • Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

Exclusion Criteria:

  • History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or Coronary Artery Bypass Graft (CABG))
  • History of liver or kidney disease
  • Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
  • History of intolerance or allergy to Aspirin or clopidogrel

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00528411


Locations
Layout table for location information
United States, Louisiana
Research Site
Baton Rouge, Louisiana, United States
United States, Maryland
Research Site
Baltimore, Maryland, United States
Research Site
Towson, Maryland, United States
United States, Ohio
Research Site
Cincinnati, Ohio, United States
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States
United States, South Dakota
Research Site
Rapid City, South Dakota, United States
United States, Texas
Research Site
Houston, Texas, United States
United Kingdom
Research Site
Sheffield, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Philip Sager, MD AstraZeneca
Principal Investigator: Paul Gurbel, MD Platelet & Thrombosis Research, LLC

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00528411     History of Changes
Other Study ID Numbers: D5130C00048
First Posted: September 12, 2007    Key Record Dates
Results First Posted: January 11, 2012
Last Update Posted: January 13, 2012
Last Verified: January 2012

Keywords provided by AstraZeneca:
Coronary artery disease
CAD
heart attack
stable angina
Stable coronary artery disease

Additional relevant MeSH terms:
Layout table for MeSH terms
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Clopidogrel
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents