Coronary Artery DiseasePhase 2NCT00528411

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

A Phase 2 study testing Ticagrelor Tablets, Clopidogrel (over encapsulated) capsule and Aspirin Tablets in people with Coronary Artery Disease, run by AstraZeneca at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Coronary Artery Disease
What is being tested?: Ticagrelor Tablets, Clopidogrel (over encapsulated) capsule and Aspirin Tablets
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 123 participants
Where: 9 sitesin 2 countries
Study dates: Oct 2007to Mar 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

United States8 sites

Research Site
Baltimore, Maryland
Research Site
Baton Rouge, Louisiana
Research Site
Cincinnati, Ohio
Research Site
Houston, Texas
Research Site
Oklahoma City, Oklahoma
Research Site
Philadelphia, Pennsylvania
Research Site
Rapid City, South Dakota
Research Site
Towson, Maryland

Other trials in United States

United Kingdom1 site

Research Site
Sheffield

Other trials in United Kingdom

About this study

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)

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.

Conditions: Coronary Artery Disease
Being tested: Ticagrelor Tablets, Clopidogrel (over encapsulated) capsule, Aspirin Tablets
Keywords: Coronary artery disease, CAD, heart attack, stable angina, Stable coronary artery disease
Medical subject headings: Coronary Artery Disease, Myocardial Infarction, Angina, Stable

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ticagrelor TabletsDrug
Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)
Clopidogrel (over encapsulated) capsuleDrug
Also called Plavix, Clopidogrel Bisulfate
Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)
Aspirin TabletsDrug
Also called ASA
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.

Study groups in NCT00528411
Study group	Role	What they receive
1	Active comparator	Aspirin + Placebo Receives: Drug: Aspirin Tablets
2	Active comparator	Aspirin + clopidogrel Receives: Drug: Clopidogrel (over encapsulated) capsule; Drug: Aspirin Tablets
3	Experimental	Aspirin + Ticagrelor Receives: Drug: Ticagrelor Tablets; Drug: Aspirin Tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 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.
Measured: At 2 hours after first dose of study drug
Slope of Extent IPA Offset Curve 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.
Measured: 4 to 72 Hours after last dose of study drug

Secondary outcomes (43)

Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 0.5 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 1 hour after first dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 4 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 8 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 24 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 0 hour before last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 2 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 4 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 8 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 24 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 48 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 72 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 120 hours - Day 5 after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 168 hours - Day 7 after last dose
Final Extent IPA Induced by 20 µM ADP at 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.
Measured: 240 hours - Day 10 after last dose
Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is measured by Spirometry, the unit is Liter.
Measured: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FEV1
FEV1 is measured by Spirometry, the unit is Liter.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)
FVC is measured by Spirometry, the unit is Liter.
Measured: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FVC
FVC is measured by Spirometry, the unit is Liter.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)
FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.
Measured: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio
FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)
FEF25-75 is measured by Spirometry, the unit is Liter/Second.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75
FEF25-75 is measured by Spirometry, the unit is Liter/Second.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)
FRC is measured by Body Box Plethysmography, the unit is Liter.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: FRC
FRC is measured by Body Box Plethysmography, the unit is Liter.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)
TLC is measured by Body Box Plethysmography, the unit is Liter.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: TLC
TLC is measured by Body Box Plethysmography, the unit is Liter.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Residual Volume (RV)
RV is measured by Body Box Plethysmography, the unit is Liter.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: RV
RV is measured by Body Box Plethysmography, the unit is Liter.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)
VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: VE
VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)
RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: RR
RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)
VT is measured by Body Box Plethysmography, the unit is Liter/Minute.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: VT
VT is measured by Body Box Plethysmography, the unit is Liter/Minute.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)
DLCOSB is measured by Body Box Plethysmography, the unit is Percent.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB
DLCOSB is measured by Body Box Plethysmography, the unit is Percent.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)
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.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: EF
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.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
NT-proBNP is measured by clinical lab, the unit is pg/mL.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP
NT-proBNP is measured by clinical lab, the unit is pg/mL.
Measured: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)
SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.
Measured: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: SpO2
SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.
Measured: 6-week post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2007Mar 2009

First posted12 Sep 2007 (estimated)
Study startOct 2007
Primary completionMar 2009
Study completionMar 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 123 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00528411
Sponsor's protocol ID: D5130C00048
Status last verified: Jan 2012
First submitted: 10 Sep 2007
Last updated: 13 Jan 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Jeong YH, Bliden KP, Antonino MJ, Park KS, Tantry US, Gurbel PA. Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies. Am Heart J. 2012 Jul;164(1):35-42. doi: 10.1016/j.ahj.2012.03.022. Epub 2012 Jun 13.
PubMed 22795280
Jeong YH, Bliden KP, Tantry US, Gurbel PA. High on-treatment platelet reactivity assessed by various platelet function tests: is the consensus-defined cut-off of VASP-P platelet reactivity index too low? J Thromb Haemost. 2012 Mar;10(3):487-9. doi: 10.1111/j.1538-7836.2011.04604.x. No abstract available.
PubMed 22212857
Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec;3(6):556-66. doi: 10.1161/CIRCGENETICS.110.958561. Epub 2010 Nov 15.
PubMed 21079055
Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, Teng R, Wei C, Tantry US, Gurbel PA; ONSET/OFFSET Investigators. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol. 2010 Jul 13;56(3):185-93. doi: 10.1016/j.jacc.2010.01.062.
PubMed 20620737
Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
PubMed 19923168

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT00528411
Acronym / sponsor ID: D5130C00048
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease, CAD, heart attack, stable angina, Stable coronary artery disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 123 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Oct 2007
Primary completion: Mar 2009 (actual)
Study completion: Mar 2009 (actual)
First posted: 12 Sep 2007 (estimated)
Results: Posted 11 Jan 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
1	Active comparator	Drug: Aspirin TabletsAspirin + Placebo
2	Active comparator	Drug: Clopidogrel (over encapsulated) capsule, Drug: Aspirin TabletsAspirin + clopidogrel
3	Experimental	Drug: Ticagrelor Tablets, Drug: Aspirin TabletsAspirin + Ticagrelor

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ticagrelor TabletsOral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)	Drug	3
Clopidogrel (over encapsulated) capsuleAlso: Plavix, Clopidogrel BisulfateOral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)	Drug	2
Aspirin TabletsAlso: ASAOral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.	Drug	1, 2, 3

Primary outcome

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.

43 secondary outcomes

Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose
Time frame: 0.5 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose
Time frame: 1 hour after first dose
Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose
Time frame: 4 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose
Time frame: 8 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose
Time frame: 24 hours after first dose
Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose
Time frame: 0 hour before last dose
Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose
Time frame: 2 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose
Time frame: 4 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose
Time frame: 8 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose
Time frame: 24 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose
Time frame: 48 hours after last dose
Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose
Time frame: 72 hours after last dose
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
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
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
Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FEV1
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)
Time frame: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FVC
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)
Time frame: Baseline
Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: FRC
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: TLC
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Residual Volume (RV)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: RV
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: VE
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: RR
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: VT
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)
Time frame: Baseline
Cardiopulmonary Parameters Post 6-week Treatment: EF
Time frame: 6-week post treatment
Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline

Results and safety

Results posted to the registry on 11 Jan 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ticagrelor	57	52
Clopidogrel	54	51
Placebo	12	11

Primary outcome: 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. Median (Inter-Quartile Range). Unit: Percentage

Measure	Ticagrelor n = 48	Clopidogrel n = 49
Value	93.15 (80.4 to 100.0)	31.05 (10.3 to 56.9)

Population analysed: Intent-to-treat analysis set: included patients who were randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

Primary outcome: 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. Least squares mean (Standard Error). Unit: Percentage/Hour

Measure	Ticagrelor n = 54	Clopidogrel n = 50
Value	-1.037 (0.076)	-0.482 (0.055)

Population analysed: Intent-to-treat analysis set: included patients who were randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

43 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ticagrelor	0 of 57 (0%)	36 of 57 (63.2%)	Not reported
Clopidogrel	0 of 54 (0%)	22 of 54 (40.7%)	Not reported
Placebo	0 of 12 (0%)	7 of 12 (58.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22795280Jeong YH, Bliden KP, Antonino MJ, Park KS, Tantry US, Gurbel PA. Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies. Am Heart J. 2012 Jul;164(1):35-42. doi: 10.1016/j.ahj.2012.03.022. Epub 2012 Jun 13.
Derived from this study: PubMed 22212857Jeong YH, Bliden KP, Tantry US, Gurbel PA. High on-treatment platelet reactivity assessed by various platelet function tests: is the consensus-defined cut-off of VASP-P platelet reactivity index too low? J Thromb Haemost. 2012 Mar;10(3):487-9. doi: 10.1111/j.1538-7836.2011.04604.x. No abstract available.
Derived from this study: PubMed 21079055Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec;3(6):556-66. doi: 10.1161/CIRCGENETICS.110.958561. Epub 2010 Nov 15.
Derived from this study: PubMed 20620737Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, Teng R, Wei C, Tantry US, Gurbel PA; ONSET/OFFSET Investigators. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol. 2010 Jul 13;56(3):185-93. doi: 10.1016/j.jacc.2010.01.062.
Derived from this study: PubMed 19923168Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Philip Sager, MD study director

AstraZeneca

Paul Gurbel, MD principal investigator

Platelet & Thrombosis Research, LLC

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ticagrelor Tablets, Clopidogrel (over encapsulated) capsule and Aspirin Tablets in people with Coronary Artery Disease, run by AstraZeneca at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00528411, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2012.