Back to resultsA Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders (RESPOND)
Primary Purpose
Stable Coronary Artery Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ticagrelor
Clopidogrel
Aspirin
Sponsored by
About this trial
This is an interventional treatment trial for Stable Coronary Artery Disease focused on measuring coronary artery disease (CAD), heart attack, stable angina
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
1
2
Arm Description
Aspirin + Ticagrelor
Aspirin + Clopidogrel
Outcomes
Primary Outcome Measures
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.)
The primary definition of response to treatment is IPA >10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. 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.
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.
The secondary definition of response to treatment is IPA >50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. 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.
Secondary Outcome Measures
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00642811
Brief Title
A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders
Acronym
RESPOND
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
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stable Coronary Artery Disease
Keywords
coronary artery disease (CAD), heart attack, stable angina
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Aspirin + Ticagrelor
Arm Title
2
Arm Type
Active Comparator
Arm Description
Aspirin + Clopidogrel
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Intervention Description
Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
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
Primary Outcome Measure Information:
Title
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.)
Description
The primary definition of response to treatment is IPA >10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. 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.
Time Frame
Day 14 and Day 28, 4 Hrs Post Dose.
Title
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.
Description
The secondary definition of response to treatment is IPA >50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. 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.
Time Frame
Day 14, and day 28, 4 hours post dose
Secondary Outcome Measure Information:
Title
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15
Description
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Time Frame
Day 15, 4 hrs post switching
Title
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28
Description
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Time Frame
4 hrs post first dose on day 28
Title
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15
Description
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Time Frame
Day 15, 4 hrs post switching
Title
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28
Description
IPA(%)=(PAb-PAt)/PAb*100. 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. Please refer to the protocol section for details about the interventions administered.
Time Frame
4 hrs post first dose on day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay Horrow, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Paul Gurbel, md
Organizational Affiliation
Platelet & Thrombosis Research, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Jonesboro
State/Province
Arkansas
Country
United States
Facility Name
Research Site
City
Ormond Beach
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Lachine
Country
Canada
Facility Name
Research Site
City
Aalborg
Country
Denmark
Facility Name
Research Site
City
Arhus
Country
Denmark
Facility Name
Research Site
City
Esbjerg
Country
Denmark
Facility Name
Research Site
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22795280
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.
Results Reference
derived
PubMed Identifier
22212857
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.
Results Reference
derived
PubMed Identifier
21079055
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.
Results Reference
derived
PubMed Identifier
20194878
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.
Results Reference
derived
Learn more about this trial
A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders
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