Coronary Artery DiseasePhase 4NCT01159639
Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting
A Phase 4 study testing Clopidogrel in people with Coronary Artery Disease and Aspirin Resistance, run by University of Zagreb at 1 site in Croatia.
Trial summary
Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Aspirin Resistance
- What is being tested?
- Clopidogrel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteCroatia
- Study dates
- Jun 2010to Feb 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Isolated coronary artery bypass grafting
- Patients older than 18 years
- Written informed consent
- Accurate antiplatelet therapy administration documentation
Who cannot join
- Missing consent
- Patients with cardiac surgical procedures other than isolated CABG
- Antiplatelet therapy other than aspirin 300 mg after CABG
- Previous PCI requiring clopidogrel therapy after CABG
- Patients with unknown preoperative anti-platelet status
- Urgent or emergent surgery
Show all 9Show fewer
- Off-pump CABG
- Re-Do CABG
- Patients younger than 18 years
Trial locations and contacts
1 site in 1 country.
Croatia1 site
Medical school Zagreb, University hospital center Zagreb
Zagreb, Croatia, 10000
About this study
Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy in the group of patients with documented aspirin resistance following CABG. Platelet function will be assessed by multiple electrode aggregometry. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early vein thrombosis is a major cause of vein graft attrition during the first month after CABG.
Bypass patency can be improved with antiplatelet therapy which is the mainstay of treatment for patients after CABG. A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been previously shown. Some patients experience thrombotic events despite continuous aspirin administration after CABG. The investigators hypothesized that low responsiveness to aspirin might be a precipitating factor for adverse thrombotic events following CABG.
Read more
Low responsiveness to ASA, as assessed by platelet function tests, varies widely among patients. The etiology of postoperative platelet hyperactivity remains to be elucidated.
In this study a new point-of-care assay named multiple electrode aggregometry (MEA) using a device called Multiplate analyzer (Dynabyte, Munich, Germany) has been utilized. It allows for rapid and standardized assessment of platelet function parameters.
This is a prospective randomized trial. The aim of the study is to document whether introduction of dual antiplatelet therapy in patients with ASA resistance will lead to a lower incidence of major adverse cardiac events (MACE) at a six month follow up. The composite endpoint will include death, non-fatal myocardial infarction, stroke and cardiac rehospitalization. All patients will receive 300 mg of ASA starting 6 hours after surgery, provided that the chest tube output is minimal. On postoperative day 4 their platelet function will be assessed using the above mentioned MEA. The patients found to be aspirin resistant will then undergo the process of randomization. The first arm will include patients with ASA resistance in whom no additional antiaggregation will be administered. In the second arm the investigators will include patients who were randomized to receive 75 mg of clopidogrel in addition to the standard antiplatelet regimen of 300 mg of ASA.
Platelet function monitoring allows for individual tailoring of the antiplatelet therapy. The goal of this study is to define whether this strategy will lead to improved patient outcomes. Both major and minor bleeding complications will be strictly monitored and reported.
- Conditions
- Coronary Artery Disease, Aspirin Resistance
- Being tested
- Clopidogrel
- Keywords
- aspirin resistance, coronary artery bypass grafting, multiple electrode aggregometry, multiplate
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
patients with inappropriate response to aspirin 300 mg after CABG, assessed by multiple electrode aggregometry are randomized to receive clopidogrel 75 mg daily dose
| Study group | Role | What they receive |
|---|---|---|
| aspirin low responders monotherapy | No intervention | patients with inappropriate response to aspirin assessed by multiple electrode aggregometry |
| aspirin low responders dual antiplatelet therapy | Active comparator | patients with inappropriate response to aspirin 300 mg therapy after CABG, randomized to receive clopidogrel 75 mg in addition to aspirin Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
MACE events
MACE: death; non-fatal myocardial infarction; stroke; cardiac rehospitalization
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2010 (estimated)
- Study startJun 2010
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zagreb
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01159639
- Sponsor's protocol ID
- 8.1-10/41-2
- Status last verified
- Jun 2010
- First submitted
- 8 Jul 2010
- Last updated
- 28 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Kopjar T, Petricevic M, Gasparovic H, Svetina L, Milicic D, Biocina B. Postoperative Atrial Fibrillation Is Associated With High On-Aspirin Platelet Reactivity. Ann Thorac Surg. 2015 Nov;100(5):1704-11. doi: 10.1016/j.athoracsur.2015.05.001. Epub 2015 Jul 26.
PubMed 26215778Petricevic M, Kopjar T, Gasparovic H, Milicic D, Svetina L, Zdilar B, Boban M, Mihaljevic MZ, Biocina B. Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639). J Thromb Thrombolysis. 2015 May;39(4):522-31. doi: 10.1007/s11239-014-1127-9.
PubMed 25095738Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Am J Cardiol. 2014 May 15;113(10):1660-7. doi: 10.1016/j.amjcard.2014.02.024. Epub 2014 Mar 1.
PubMed 24666617Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]. Trials. 2012 Aug 25;13:148. doi: 10.1186/1745-6215-13-148.
PubMed 22920307
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting
- ClinicalTrials.gov ID
- NCT01159639
- Acronym / sponsor ID
- 8.1-10/41-2
- Conditions
- Coronary Artery Disease, Aspirin Resistance
- Keywords
- aspirin resistance, coronary artery bypass grafting, multiple electrode aggregometry, multiplate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of ZagrebUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 9 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy in the group of patients with documented aspirin resistance following CABG. Platelet function will be assessed by multiple electrode aggregometry. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early vein thrombosis is a major cause of vein graft attrition during the first month after CABG.
Bypass patency can be improved with antiplatelet therapy which is the mainstay of treatment for patients after CABG. A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been previously shown. Some patients experience thrombotic events despite continuous aspirin administration after CABG. The investigators hypothesized that low responsiveness to aspirin might be a precipitating factor for adverse thrombotic events following CABG.
Low responsiveness to ASA, as assessed by platelet function tests, varies widely among patients. The etiology of postoperative platelet hyperactivity remains to be elucidated.
In this study a new point-of-care assay named multiple electrode aggregometry (MEA) using a device called Multiplate analyzer (Dynabyte, Munich, Germany) has been utilized. It allows for rapid and standardized assessment of platelet function parameters.
This is a prospective randomized trial. The aim of the study is to document whether introduction of dual antiplatelet therapy in patients with ASA resistance will lead to a lower incidence of major adverse cardiac events (MACE) at a six month follow up. The composite endpoint will include death, non-fatal myocardial infarction, stroke and cardiac rehospitalization. All patients will receive 300 mg of ASA starting 6 hours after surgery, provided that the chest tube output is minimal. On postoperative day 4 their platelet function will be assessed using the above mentioned MEA. The patients found to be aspirin resistant will then undergo the process of randomization. The first arm will include patients with ASA resistance in whom no additional antiaggregation will be administered. In the second arm the investigators will include patients who were randomized to receive 75 mg of clopidogrel in addition to the standard antiplatelet regimen of 300 mg of ASA.
Platelet function monitoring allows for individual tailoring of the antiplatelet therapy. The goal of this study is to define whether this strategy will lead to improved patient outcomes. Both major and minor bleeding complications will be strictly monitored and reported.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| aspirin low responders monotherapy | No intervention | –patients with inappropriate response to aspirin assessed by multiple electrode aggregometry |
| aspirin low responders dual antiplatelet therapy | Active comparator | Drug: Clopidogrelpatients with inappropriate response to aspirin 300 mg therapy after CABG, randomized to receive clopidogrel 75 mg in addition to aspirin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Isolated coronary artery bypass grafting
- Patients older than 18 years
- Written informed consent
- Accurate antiplatelet therapy administration documentation
Key exclusion criteria (9 listed)
- Missing consent
- Patients with cardiac surgical procedures other than isolated CABG
- Antiplatelet therapy other than aspirin 300 mg after CABG
- Previous PCI requiring clopidogrel therapy after CABG
- Patients with unknown preoperative anti-platelet status
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 |
|---|---|---|
| Clopidogrelpatients with inappropriate response to aspirin 300 mg after CABG, assessed by multiple electrode aggregometry are randomized to receive clopidogrel 75 mg daily dose | Drug | aspirin low responders dual antiplatelet therapy |
Primary outcome
MACE events
Time frame: 6 months
MACE: death; non-fatal myocardial infarction; stroke; cardiac rehospitalization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2013.
- Derived from this study: PubMed 26215778Kopjar T, Petricevic M, Gasparovic H, Svetina L, Milicic D, Biocina B. Postoperative Atrial Fibrillation Is Associated With High On-Aspirin Platelet Reactivity. Ann Thorac Surg. 2015 Nov;100(5):1704-11. doi: 10.1016/j.athoracsur.2015.05.001. Epub 2015 Jul 26.
- Derived from this study: PubMed 25095738Petricevic M, Kopjar T, Gasparovic H, Milicic D, Svetina L, Zdilar B, Boban M, Mihaljevic MZ, Biocina B. Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639). J Thromb Thrombolysis. 2015 May;39(4):522-31. doi: 10.1007/s11239-014-1127-9.
- Derived from this study: PubMed 24666617Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients following coronary artery bypass grafting. Am J Cardiol. 2014 May 15;113(10):1660-7. doi: 10.1016/j.amjcard.2014.02.024. Epub 2014 Mar 1.
- Derived from this study: PubMed 22920307Gasparovic H, Petricevic M, Kopjar T, Djuric Z, Svetina L, Biocina B. Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]. Trials. 2012 Aug 25;13:148. doi: 10.1186/1745-6215-13-148.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clopidogrel in people with Coronary Artery Disease and Aspirin Resistance, run by University of Zagreb at 1 site in Croatia.
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 4 inclusion and 9 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 28 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MACE events (time frame: 6 months). 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 NCT01159639, 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 28 Aug 2013.