Acute Coronary SyndromePhase 4PRU-MATRIXNCT01477775
Customized Choice of Oral P2Y12 Receptor Blocker
A Phase 4 study testing Oral P2Y12 receptor blocker and Customized choice for the oral P2Y12 receptor blocker in people with Acute Coronary Syndrome and Coronary Angioplasty, run by Italian Society of Invasive Cardiology at 11 sites in Italy.
Trial summary
A subset of patients recruited in the main MATRIX study will be randomized after intervention but before discharge to standard of care (the treating physician will decide which oral P2Y12 inhibitor will be added on top of aspirin) versus a customized approach based on an algorithm which integrates phenotypic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Coronary Syndrome, Coronary Angioplasty
- What is being tested?
- Oral P2Y12 receptor blocker and Customized choice for the oral P2Y12 receptor blocker
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,000 participants
- Where
- 11 sitesItaly
- Study dates
- Jan 2012to Dec 2015
- 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
- patients recruited in the main MATRIX study who underwent coronary angioplasty with stent placement.
Who cannot join
- unwillingness to sign this sub study specific informed consent
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Italy11 sites, 8 recruiting
- Active, not recruiting
Spedali Civili di Brescia
Brescia
- Recruiting
Azienda USL Sirai
Carbonia
Salvatore Ierna, MD
Salvatore Ierna, MD
- Active, not recruiting
Azienda Ospedaliera Pugliese Ciaccio
Catanzaro, Calabria, 88100
- Recruiting
University Hospital of Ferrara
Ferrara, Ferrara, 44100
Marco Valgimigli, MD, PhD, 3356478877 ext. +39, vlgmrc@unife.it
Gianluca Campo, MD
- Active, not recruiting
Ospedale di Lodi
Lodi
- Recruiting
Azienda Ospedaliera Fatebenefratelli e Oftalmico
Milan, MI, 20121
B. Cortese, MD, +393347298103, bcortese@gmail.com
Bernardo Cortese, MD
- Recruiting
Ospedale dei Colli, Cardiologia SUN
Naples
Paolo Calabrò, MD PhD
Paolo Calabrò, MD
- Recruiting
Ospedale degli Infermi di Rimini
Rimini
Andrea Santarelli, MD
Andrea Santarelli, MD
- Recruiting
Ospedale San Giovanni Bosco
Torino
Roberto Garbo, MD
Roberto Garbo, MD
- Recruiting
A. O. Ospedale Civile di Vimercate
Vimercate
Stefano Garducci, MD
Stefano Garducci, MD
- Recruiting
Policlinico San Marco
Zingonia
Nicoletta De Cesare, MD
Nicoletta De Casare, MD
About this study
Official title: Customized Choice of P2Y12 Oral Receptor Blocker Based on Phenotype Assessment Via Point of Care Testing
A subset of patients recruited in the main MATRIX study will be randomized after intervention but before discharge to standard of care (the treating physician will decide which oral P2Y12 inhibitor will be added on top of aspirin) versus a customized approach based on an algorithm which integrates phenotypic information, including but not limited to residual on-treatment platelet reactivity assessed via VerifyNow P2Y12 Assay.
Read the detailed description
Up to 20-30% of clopidogrel treated patients do not adequately respond to the drug and are at higher risk for ischemic events including death, myocardial infarction, stroke and stent thrombosis.
Residual high on-treatment platelet reactivity while the patient is on clopidogrel depends on a complex interplay of phenotypic (spontaneous platelet reactivity, inflammatory status, acuity of the clinical presentation, age, renal function) and genetic variables.
Two main Loss of function alleles have been identified: 1) CYP450 2C19*2 is present in around 25% of the Caucasian population and result in a lower amount of clopidogrel active metabolite. Carriers of 2C19*2 are at higher risk for death or MI and 2.7 fold increase in the risk of stent thrombosis if treated with conventional clopidogrel; 2) ABCB-1 C carriers have reduced clopidogrel absorption and they have similarly been shown to be at higher risk for ischemic adverse events if treated with clopidogrel. Many investigators have recently shown however, that the positive predictive value of genetic testing alone at the time of PCI is limited and the knowledge of genetic status alone with respect to the two previously described loss of function alleles is only poorly able to identify to long-term clopidogrel poor responders. An Algorithm has therefore been developed, combining phenotype information which has been shown to risk stratify both ischemic and bleeding events up to one year follow-up in PCI patients.
This algorithm has been developed from a single center retrospective registry. To prospectively validate it in the context of a prospective multicenter study, the first 320 patients recruited in the present study will undergo phenotype at discharge and at 30 days and genotype assessment at the time of randomization, irrespective of the group which they have been assigned to (i.e. standard of care or gene and phenotype). The hypothesis behind this mechanistic sub-study is that the use of this combined phenotype-genotype algorithm will increase the proportion of patients at 30 days who will be in the therapeutic range according to PRU values from 50% in the standard of care versus 70% in the gene and phenotype group.
- Conditions
- Acute Coronary Syndrome, Coronary Angioplasty
- Being tested
- Oral P2Y12 receptor blocker, Customized choice for the oral P2Y12 receptor blocker
- Keywords
- myocardial infarction, coronary stent, Oral P2Y12 receptor blocker, Platelet reactivity units (PRU)
- Medical subject headings
- Acute Coronary Syndrome, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral P2Y12 receptor blockerDrug
Free choice among clopidogrel, prasugrel or ticagrelor
Customized choice for the oral P2Y12 receptor blockerDrug
one drug among clopidogrel, prasugrel or ticagrelor based on an algorithm integrating phenotype information.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | The treating physician will be left free to give the oral P2Y12 receptor blocker, including clopidogrel,prasugrel or ticagrelor, which according to his/her clinical judgement is most appropriate for the individual patient. Receives: Drug: Oral P2Y12 receptor blocker |
| Customized choice of the oral P2Y12 receptor blocker | Experimental | The choice of the oral P2Y12 receptor blocker will be based on an algorithm which integrates phenotype information, including but not limited to residual on-treatment platelet reactivity assessed via Verifynow P2Y12 assay. Receives: Drug: Customized choice for the oral P2Y12 receptor blocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiovascular death, myocardial infarction, stroke or BARC defined bleeding type 2, 3 or 5
The time to first occurrence of any of the variables listed above will be reported as primary study outcome.
Measured: 1 year
Proportion of patients in the therapeutic range for residual P2Y12 pathway activity according to PRU values.
We expect that the prospective use of the previously generated combined phenotype and genotype algorithm will result in an higher proportion of patients being in the therapeutic range with respect to the P2Y12 residual activity (70%) as compared to patients in who the P2Y12 inhibitor is left to the discretion of the treating physician. The first 320 patients recruited in the present study will participate into this mechanistic sub-study.
Measured: 30 days
Secondary outcomes (9)
Overall death
Measured: 1
cardiovascular death
Measured: 1 year
myocardial infarction
Measured: 1 year
stroke
Measured: 1 year
BARC bleeding type 2
Measured: 1 year
BARC bleeding type 3
Measured: 1 year
BARC bleeding type 5
Measured: 1 year
Bleeding classified according to the Bleedscore
Measured: 1 year
Stent thrombosis
Stent thrombosis will be reported according to the ARC classification
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2015 (estimated)
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 Acute Coronary SyndromeStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Italian Society of Invasive Cardiology
- Sponsor type
- University, hospital or other
- Collaborators
- Eustrategy
- Responsible party
- Sponsor
- Investigators
- Marco Valgimigli, MD, PhD, Principal investigator, University Hospital of Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01477775
- Sponsor's protocol ID
- RFBU 13-I-PRU
- Acronym
- PRU-MATRIX
- Status last verified
- Sep 2014
- First submitted
- 27 Oct 2011
- Last updated
- 3 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Campo G, Parrinello G, Ferraresi P, Lunghi B, Tebaldi M, Miccoli M, Marchesini J, Bernardi F, Ferrari R, Valgimigli M. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83. doi: 10.1016/j.jacc.2010.12.047.
PubMed 21679849Campo G, Ferraresi P, Marchesini J, Bernardi F, Valgimigli M. Relationship between paraoxonase Q192R gene polymorphism and on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention. J Thromb Haemost. 2011 Oct;9(10):2106-8. doi: 10.1111/j.1538-7836.2011.04457.x. No abstract available.
PubMed 21819538Campo G, Miccoli M, Tebaldi M, Marchesini J, Fileti L, Monti M, Valgimigli M, Ferrari R. Genetic determinants of on-clopidogrel high platelet reactivity. Platelets. 2011;22(6):399-407. doi: 10.3109/09537104.2011.579648. Epub 2011 May 31.
PubMed 21627411Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A, Angiolillo DJ, Sabate M, Hamon M, Repetto A, Colangelo S, Brugaletta S, Parrinello G, Percoco G, Ferrari R; Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R) Investigators. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation. 2009 Jun 30;119(25):3215-22. doi: 10.1161/CIRCULATIONAHA.108.833236. Epub 2009 Jun 15.
PubMed 19528337
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Customized Choice of P2Y12 Oral Receptor Blocker Based on Phenotype Assessment Via Point of Care Testing
- ClinicalTrials.gov ID
- NCT01477775
- Acronym / sponsor ID
- PRU-MATRIX / RFBU 13-I-PRU
- Conditions
- Acute Coronary Syndrome, Coronary Angioplasty
- Keywords
- myocardial infarction, coronary stent, Oral P2Y12 receptor blocker, Platelet reactivity units (PRU)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4,000 participants (estimated)
- Lead sponsor
- Italian Society of Invasive CardiologyUniversity, hospital or other
- Collaborators
- Eustrategy
- Study start
- Jan 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 23 Nov 2011 (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.
A subset of patients recruited in the main MATRIX study will be randomized after intervention but before discharge to standard of care (the treating physician will decide which oral P2Y12 inhibitor will be added on top of aspirin) versus a customized approach based on an algorithm which integrates phenotypic information, including but not limited to residual on-treatment platelet reactivity assessed via VerifyNow P2Y12 Assay.
Detailed description
Up to 20-30% of clopidogrel treated patients do not adequately respond to the drug and are at higher risk for ischemic events including death, myocardial infarction, stroke and stent thrombosis.
Residual high on-treatment platelet reactivity while the patient is on clopidogrel depends on a complex interplay of phenotypic (spontaneous platelet reactivity, inflammatory status, acuity of the clinical presentation, age, renal function) and genetic variables.
Two main Loss of function alleles have been identified: 1) CYP450 2C19*2 is present in around 25% of the Caucasian population and result in a lower amount of clopidogrel active metabolite. Carriers of 2C19*2 are at higher risk for death or MI and 2.7 fold increase in the risk of stent thrombosis if treated with conventional clopidogrel; 2) ABCB-1 C carriers have reduced clopidogrel absorption and they have similarly been shown to be at higher risk for ischemic adverse events if treated with clopidogrel. Many investigators have recently shown however, that the positive predictive value of genetic testing alone at the time of PCI is limited and the knowledge of genetic status alone with respect to the two previously described loss of function alleles is only poorly able to identify to long-term clopidogrel poor responders. An Algorithm has therefore been developed, combining phenotype information which has been shown to risk stratify both ischemic and bleeding events up to one year follow-up in PCI patients.
This algorithm has been developed from a single center retrospective registry. To prospectively validate it in the context of a prospective multicenter study, the first 320 patients recruited in the present study will undergo phenotype at discharge and at 30 days and genotype assessment at the time of randomization, irrespective of the group which they have been assigned to (i.e. standard of care or gene and phenotype). The hypothesis behind this mechanistic sub-study is that the use of this combined phenotype-genotype algorithm will increase the proportion of patients at 30 days who will be in the therapeutic range according to PRU values from 50% in the standard of care versus 70% in the gene and phenotype group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Drug: Oral P2Y12 receptor blockerThe treating physician will be left free to give the oral P2Y12 receptor blocker, including clopidogrel,prasugrel or ticagrelor, which according to his/her clinical judgement is most appropriate for the individual patient. |
| Customized choice of the oral P2Y12 receptor blocker | Experimental | Drug: Customized choice for the oral P2Y12 receptor blockerThe choice of the oral P2Y12 receptor blocker will be based on an algorithm which integrates phenotype information, including but not limited to residual on-treatment platelet reactivity assessed via Verifynow P2Y12 assay. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- patients recruited in the main MATRIX study who underwent coronary angioplasty with stent placement.
Key exclusion criteria (1 listed)
- unwillingness to sign this sub study specific informed consent
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 |
|---|---|---|
| Oral P2Y12 receptor blockerFree choice among clopidogrel, prasugrel or ticagrelor | Drug | Standard of Care |
| Customized choice for the oral P2Y12 receptor blockerone drug among clopidogrel, prasugrel or ticagrelor based on an algorithm integrating phenotype information. | Drug | Customized choice of the oral P2Y12 receptor blocker |
Primary outcome
Cardiovascular death, myocardial infarction, stroke or BARC defined bleeding type 2, 3 or 5
Time frame: 1 year
The time to first occurrence of any of the variables listed above will be reported as primary study outcome.
Proportion of patients in the therapeutic range for residual P2Y12 pathway activity according to PRU values.
Time frame: 30 days
We expect that the prospective use of the previously generated combined phenotype and genotype algorithm will result in an higher proportion of patients being in the therapeutic range with respect to the P2Y12 residual activity (70%) as compared to patients in who the P2Y12 inhibitor is left to the discretion of the treating physician. The first 320 patients recruited in the present study will participate into this mechanistic sub-study.
9 secondary outcomes
Overall death
Time frame: 1
cardiovascular death
Time frame: 1 year
myocardial infarction
Time frame: 1 year
stroke
Time frame: 1 year
BARC bleeding type 2
Time frame: 1 year
BARC bleeding type 3
Time frame: 1 year
BARC bleeding type 5
Time frame: 1 year
Bleeding classified according to the Bleedscore
Time frame: 1 year
Stent thrombosis
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2014.
- Background: PubMed 21679849Campo G, Parrinello G, Ferraresi P, Lunghi B, Tebaldi M, Miccoli M, Marchesini J, Bernardi F, Ferrari R, Valgimigli M. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83. doi: 10.1016/j.jacc.2010.12.047.
- Background: PubMed 21819538Campo G, Ferraresi P, Marchesini J, Bernardi F, Valgimigli M. Relationship between paraoxonase Q192R gene polymorphism and on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention. J Thromb Haemost. 2011 Oct;9(10):2106-8. doi: 10.1111/j.1538-7836.2011.04457.x. No abstract available.
- Background: PubMed 21627411Campo G, Miccoli M, Tebaldi M, Marchesini J, Fileti L, Monti M, Valgimigli M, Ferrari R. Genetic determinants of on-clopidogrel high platelet reactivity. Platelets. 2011;22(6):399-407. doi: 10.3109/09537104.2011.579648. Epub 2011 May 31.
- Background: PubMed 19528337Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A, Angiolillo DJ, Sabate M, Hamon M, Repetto A, Colangelo S, Brugaletta S, Parrinello G, Percoco G, Ferrari R; Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R) Investigators. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation. 2009 Jun 30;119(25):3215-22. doi: 10.1161/CIRCULATIONAHA.108.833236. Epub 2009 Jun 15.
Related trials for Acute Coronary Syndrome
Recruiting
CT Stress Myocardial Perfusion, Fractional Flow Reserve and Angiography in Patients With Stable Chest Pain Syndromes
Coronary Artery Disease, Chest Syndrome
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
RecruitingPhase 4
Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome
Acute Coronary Syndromes, STEMI
Recruiting
AI-Assisted Interpretation of Cardiac CT in the Emergency Department
Chest Pain, Acute Coronary Syndrome
Enrolling by invitation
Optical Coherence Tomography in Acute Vessel Evaluation
Ischemic Heart Disease, Ischemic Coronary Artery Disease
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.
Marco Valgimigli, MD, PhD principal investigator
University Hospital of Ferrara
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral P2Y12 receptor blocker and Customized choice for the oral P2Y12 receptor blocker in people with Acute Coronary Syndrome and Coronary Angioplasty, run by Italian Society of Invasive Cardiology at 11 sites in Italy.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 3 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Valgimigli, MD, PhD (3356478877 ext. +39, vlgmrc@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiovascular death, myocardial infarction, stroke or BARC defined bleeding type 2, 3 or 5 (time frame: 1 year). 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 NCT01477775, 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 3 Sep 2014.