Stable Coronary Artery DiseasePhase 2RESPONDNCT00642811
A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders
A Phase 2 study testing Ticagrelor, Clopidogrel and Aspirin in people with Stable Coronary Artery Disease, run by AstraZeneca at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stable Coronary Artery Disease
- What is being tested?
- Ticagrelor, Clopidogrel and Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 10 sitesin 4 countries
- Study dates
- May 2008to 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
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States4 sites
Research Site
Baltimore, Maryland
Research Site
Cincinnati, Ohio
Research Site
Jonesboro, Arkansas
Research Site
Ormond Beach, Florida
About this study
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]
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.
- Conditions
- Stable Coronary Artery Disease
- Being tested
- Ticagrelor, Clopidogrel, Aspirin
- Keywords
- coronary artery disease (CAD), heart attack, stable angina
- 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.
TicagrelorDrug
Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks
ClopidogrelDrug
Also called Plavix
(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks
AspirinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Aspirin + Ticagrelor Receives: Drug: Ticagrelor; Drug: Aspirin |
| 2 | Active comparator | Aspirin + Clopidogrel Receives: Drug: Clopidogrel; Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 14 and Day 28, 4 Hrs Post Dose.
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.
Measured: Day 14, and day 28, 4 hours post dose
Secondary outcomes (4)
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.
Measured: Day 15, 4 hrs post switching
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.
Measured: 4 hrs post first dose on day 28
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.
Measured: Day 15, 4 hrs post switching
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.
Measured: 4 hrs post first dose on day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2008 (estimated)
- Study startMay 2008
- 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 (4)Papers the sponsor has linked to this study.
- Other trials for Stable 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jay Horrow, MD, Study director, AstraZenecaPaul Gurbel, md, Principal investigator, Platelet & Thrombosis Research, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00642811
- Sponsor's protocol ID
- D5130C00030
- Acronym
- RESPOND
- Status last verified
- Aug 2011
- First submitted
- 19 Mar 2008
- Last updated
- 4 Oct 2011
- 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 22795280Jeong 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 22212857Tantry 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 21079055Gurbel 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.
PubMed 20194878
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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]
- ClinicalTrials.gov ID
- NCT00642811
- Acronym / sponsor ID
- RESPOND / D5130C00030
- Conditions
- Stable Coronary Artery Disease
- Keywords
- coronary artery disease (CAD), heart attack, stable angina
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 25 Mar 2008 (estimated)
- Results
- Posted 4 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Ticagrelor, Drug: AspirinAspirin + Ticagrelor |
| 2 | Active comparator | Drug: Clopidogrel, Drug: AspirinAspirin + Clopidogrel |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
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))
- 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
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 |
|---|---|---|
| TicagrelorTablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks | Drug | 1 |
| ClopidogrelAlso: Plavix(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks | Drug | 2 |
| AspirinTablets, 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 | Drug | 1, 2 |
Primary outcome
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.)
Time frame: Day 14 and Day 28, 4 Hrs Post Dose.
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.
Time frame: Day 14, and day 28, 4 hours post dose
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.
4 secondary outcomes
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15
Time frame: Day 15, 4 hrs post switching
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28
Time frame: 4 hrs post first dose on day 28
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15
Time frame: Day 15, 4 hrs post switching
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28
Time frame: 4 hrs post first dose on day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2011.
- 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 20194878Gurbel 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.
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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.
Jay Horrow, MD study director
AstraZeneca
Paul Gurbel, md principal investigator
Platelet & Thrombosis Research, LLC
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ticagrelor, Clopidogrel and Aspirin in people with Stable Coronary Artery Disease, run by AstraZeneca at 10 sites in 4 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 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Denmark, Canada, 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 4 Oct 2011). 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?
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.) (time frame: Day 14 and Day 28, 4 Hrs Post Dose.). 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 NCT00642811, which also lists 4 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 4 Oct 2011.