Clinical trial NCT00528411: A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease
CAD
heart attack
stable angina
Stable coronary artery disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2007-09-12
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose
timeFrame: At 2 hours after first dose of study drug
measure: Slope of Extent IPA Offset Curve 4 to 72 Hours After Last Dose of Study Drug
timeFrame: 4 to 72 Hours after last dose of study drug
Secondary outcomes:
measure: Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose
timeFrame: 0.5 hours after first dose
measure: Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose
timeFrame: 1 hour after first dose
measure: Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose
timeFrame: 4 hours after first dose
measure: Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose
timeFrame: 8 hours after first dose
measure: Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose
timeFrame: 24 hours after first dose
measure: Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose
timeFrame: 0 hour before last dose
measure: Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose
timeFrame: 2 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose
timeFrame: 4 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose
timeFrame: 8 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose
timeFrame: 24 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose
timeFrame: 48 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose
timeFrame: 72 hours after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose
timeFrame: 120 hours - Day 5 after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose
timeFrame: 168 hours - Day 7 after last dose
measure: Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose
timeFrame: 240 hours - Day 10 after last dose
measure: Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline
measure: Cardiopulmonary Parameters at Post 6-week Treatment: FEV1
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)
timeFrame: Baseline
measure: Cardiopulmonary Parameters at Post 6-week Treatment: FVC
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)
timeFrame: Baseline
measure: Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: FRC
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: TLC
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Residual Volume (RV)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: RV
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: VE
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: RR
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: VT
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: EF
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP
timeFrame: 6-week post treatment
measure: Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)
timeFrame: Baseline
measure: Cardiopulmonary Parameters Post 6-week Treatment: SpO2
timeFrame: 6-week post treatment
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Houston
country: United States
facility: Research Site
state: Texas
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Philip Sager, MD
role: STUDY_DIRECTOR
affiliation: Platelet & Thrombosis Research, LLC
name: Paul Gurbel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.