Clinical trial NCT00642811: A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders
Official title: A Randomised, Double-Blind, Outpatient, Crossover Study of the Anti-platelet Effects of Ticagrelor Compared With Clopidogrel in Patients With Stable Coronary Artery Disease Previously Identified as Clopidogrel Non-responders or Responders [RESPOND]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stable Coronary Artery Disease
Keywords: coronary artery disease (CAD)
heart attack
stable angina
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-03-25
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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 the effect of Ticagrelor on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel.


Eligibility criteria: Inclusion Criteria:

* Patients with documented stable Coronary Artery Disease (CAD) (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))
* Any acute or chronic unstable condition in the past 30 days
* 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: Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.)
timeFrame: Day 14 and Day 28, 4 Hrs Post Dose.
measure: Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.
timeFrame: Day 14, and day 28, 4 hours post dose
Secondary outcomes:
measure: Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15
timeFrame: Day 15, 4 hrs post switching
measure: Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28
timeFrame: 4 hrs post first dose on day 28
measure: Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15
timeFrame: Day 15, 4 hrs post switching
measure: Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28
timeFrame: 4 hrs post first dose on day 28
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Research Site
state: Arkansas
city: Ormond Beach
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Lachine
country: Canada
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Arhus
country: Denmark
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jay Horrow, 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: Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. doi: 10.1161/CIRCULATIONAHA.109.919456. Epub 2010 Mar 1.