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

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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

Tracking Information
First Submitted Date  ICMJE September 10, 2007
First Posted Date  ICMJE September 12, 2007
Results First Submitted Date  ICMJE January 27, 2011
Results First Posted Date  ICMJE January 11, 2012
Last Update Posted Date January 13, 2012
Study Start Date  ICMJE October 2007
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 12, 2012)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 11, 2007)
To det. the onset and offset of antiplatelet effect of AZD6140 compared to clopidogrel by eval. of the % IPA by LTA at 2 hrs post 1st dose of study drug and by eval. of the diff. in slope of IPA effect curve by LTA after the last dose of study drug.
Change History Complete list of historical versions of study NCT00528411 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2012)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline ]
    FEV1 is measured by Spirometry, the unit is Liter.
  • Cardiopulmonary Parameters at Post 6-week Treatment: FEV1 [ Time Frame: 6-week post treatment ]
    FEV1 is measured by Spirometry, the unit is Liter.
  • Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC) [ Time Frame: Baseline ]
    FVC is measured by Spirometry, the unit is Liter.
  • Cardiopulmonary Parameters at Post 6-week Treatment: FVC [ Time Frame: 6-week post treatment ]
    FVC is measured by Spirometry, the unit is Liter.
  • 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.
  • 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.
  • 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.
  • 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.
  • Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC) [ Time Frame: Baseline ]
    FRC is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters Post 6-week Treatment: FRC [ Time Frame: 6-week post treatment ]
    FRC is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC) [ Time Frame: Baseline ]
    TLC is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters Post 6-week Treatment: TLC [ Time Frame: 6-week post treatment ]
    TLC is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters at Baseline: Residual Volume (RV) [ Time Frame: Baseline ]
    RV is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters Post 6-week Treatment: RV [ Time Frame: 6-week post treatment ]
    RV is measured by Body Box Plethysmography, the unit is Liter.
  • Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE) [ Time Frame: Baseline ]
    VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute
  • 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
  • Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR) [ Time Frame: Baseline ]
    RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.
  • 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.
  • Cardiopulmonary Parameters at Baseline: Tidal Volume (VT) [ Time Frame: Baseline ]
    VT is measured by Body Box Plethysmography, the unit is Liter/Minute.
  • 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.
  • 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.
  • Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB [ Time Frame: 6-week post treatment ]
    DLCOSB is measured by Body Box Plethysmography, the unit is Percent.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2007)
To evaluate the PK/PD relationship of AZD6140 and its active metabolite; to determine the effect on platelet aggregation of AZD6140 compared to clopidogrel; to assess the overall safety and tolerability of AZD6140 compared to clopidogrel and placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Coronary Artery Disease
Intervention  ICMJE
  • Drug: Ticagrelor Tablets
    Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)
  • 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
Study Arms  ICMJE
  • Active Comparator: 1
    Aspirin + Placebo
    Intervention: Drug: Aspirin Tablets
  • Active Comparator: 2
    Aspirin + clopidogrel
    Interventions:
    • Drug: Clopidogrel (over encapsulated) capsule
    • Drug: Aspirin Tablets
  • Experimental: 3
    Aspirin + Ticagrelor
    Interventions:
    • Drug: Ticagrelor Tablets
    • Drug: Aspirin Tablets
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 6, 2011)
123
Original Estimated Enrollment  ICMJE
 (submitted: September 11, 2007)
150
Actual Study Completion Date  ICMJE March 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00528411
Other Study ID Numbers  ICMJE D5130C00048
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Philip Sager, MD AstraZeneca
Principal Investigator: Paul Gurbel, MD Platelet & Thrombosis Research, LLC
PRS Account AstraZeneca
Verification Date January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP