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

Phase 2
Completed
Conditions
Coronary Artery Disease
Interventions
Registration Number
NCT00528411
Lead Sponsor
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
123
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2Clopidogrel (over encapsulated) capsuleAspirin + clopidogrel
2Aspirin TabletsAspirin + clopidogrel
3Aspirin TabletsAspirin + Ticagrelor
1Aspirin TabletsAspirin + Placebo
3Ticagrelor TabletsAspirin + Ticagrelor
Primary Outcome Measures
NameTimeMethod
Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First DoseAt 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 Drug4 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
NameTimeMethod
Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose0.5 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 Dose1 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 Dose4 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.

Cardiopulmonary Parameters at Post 6-week Treatment: FEV16-week post treatment

FEV1 is measured by Spirometry, the unit is Liter.

Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose8 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 Dose24 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 Dose0 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 Dose2 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 Dose4 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 Dose8 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 Dose24 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 Dose48 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 Dose72 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 Dose120 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 Dose168 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 Dose240 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)Baseline

FEV1 is measured by Spirometry, the unit is Liter.

Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)Baseline

FVC is measured by Spirometry, the unit is Liter.

Cardiopulmonary Parameters at Post 6-week Treatment: FVC6-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)Baseline

FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.

Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio6-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)Baseline

FEF25-75 is measured by Spirometry, the unit is Liter/Second.

Cardiopulmonary Parameters Post 6-week Treatment: FEF25-756-week post treatment

FEF25-75 is measured by Spirometry, the unit is Liter/Second.

Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)Baseline

FRC is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters Post 6-week Treatment: FRC6-week post treatment

FRC is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)Baseline

TLC is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters Post 6-week Treatment: TLC6-week post treatment

TLC is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters at Baseline: Residual Volume (RV)Baseline

RV is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters Post 6-week Treatment: RV6-week post treatment

RV is measured by Body Box Plethysmography, the unit is Liter.

Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)Baseline

VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute

Cardiopulmonary Parameters Post 6-week Treatment: VE6-week post treatment

VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute

Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)Baseline

RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.

Cardiopulmonary Parameters Post 6-week Treatment: RR6-week post treatment

RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.

Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)Baseline

VT is measured by Body Box Plethysmography, the unit is Liter/Minute.

Cardiopulmonary Parameters Post 6-week Treatment: VT6-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)Baseline

DLCOSB is measured by Body Box Plethysmography, the unit is Percent.

Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB6-week post treatment

DLCOSB is measured by Body Box Plethysmography, the unit is Percent.

Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)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: EF6-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)Baseline

NT-proBNP is measured by clinical lab, the unit is pg/mL.

Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP6-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)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: SpO26-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.

Trial Locations

Locations (1)

Research Site

🇬🇧

Sheffield, United Kingdom

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