Customized Choice of Oral P2Y12 Receptor Blocker (PRU-MATRIX)
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| ClinicalTrials.gov Identifier: NCT01477775 |
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Recruitment Status : Unknown
Verified September 2014 by Italian Society of Invasive Cardiology.
Recruitment status was: Recruiting
First Posted : November 23, 2011
Last Update Posted : September 3, 2014
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Coronary Syndrome Coronary Angioplasty | Drug: Oral P2Y12 receptor blocker Drug: Customized choice for the oral P2Y12 receptor blocker | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 4000 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Customized Choice of P2Y12 Oral Receptor Blocker Based on Phenotype Assessment Via Point of Care Testing |
| Study Start Date : | January 2012 |
| Estimated Primary Completion Date : | December 2014 |
| Estimated Study Completion Date : | December 2015 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Standard of Care
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.
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Drug: Oral P2Y12 receptor blocker
Free choice among clopidogrel, prasugrel or ticagrelor |
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Experimental: Customized choice of the oral P2Y12 receptor blocker
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.
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Drug: Customized choice for the oral P2Y12 receptor blocker
one drug among clopidogrel, prasugrel or ticagrelor based on an algorithm integrating phenotype information. |
- 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.
- 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 ]Stent thrombosis will be reported according to the ARC classification
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- patients recruited in the main MATRIX study who underwent coronary angioplasty with stent placement.
Exclusion Criteria:
- unwillingness to sign this sub study specific informed consent
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01477775
| Contact: Marco Valgimigli, MD, PhD | 3356478877 ext +39 | vlgmrc@unife.it | |
| Contact: Maria Salomone, MD | 3357378767 ext +39 | m.salomone@dimensione-ricerca.com |
| Italy | |
| Azienda Ospedaliera Pugliese Ciaccio | Active, not recruiting |
| Catanzaro, Calabria, Italy, 88100 | |
| Azienda Ospedaliera Fatebenefratelli e Oftalmico | Recruiting |
| Milano, MI, Italy, 20121 | |
| Contact: B. Cortese, MD +393347298103 bcortese@gmail.com | |
| Principal Investigator: Bernardo Cortese, MD | |
| Spedali Civili di Brescia | Active, not recruiting |
| Brescia, Italy | |
| Azienda USL Sirai | Recruiting |
| Carbonia, Italy | |
| Contact: Salvatore Ierna, MD | |
| Principal Investigator: Salvatore Ierna, MD | |
| University Hospital of Ferrara | Recruiting |
| Ferrara, Italy, 44100 | |
| Contact: Marco Valgimigli, MD, PhD 3356478877 ext +39 vlgmrc@unife.it | |
| Principal Investigator: Gianluca Campo, MD | |
| Ospedale di Lodi | Active, not recruiting |
| Lodi, Italy | |
| Ospedale dei Colli, Cardiologia SUN | Recruiting |
| Naples, Italy | |
| Contact: Paolo Calabrò, MD PhD | |
| Principal Investigator: Paolo Calabrò, MD | |
| Ospedale degli Infermi di Rimini | Recruiting |
| Rimini, Italy | |
| Contact: Andrea Santarelli, MD | |
| Principal Investigator: Andrea Santarelli, MD | |
| Ospedale San Giovanni Bosco | Recruiting |
| Torino, Italy | |
| Contact: Roberto Garbo, MD | |
| Principal Investigator: Roberto Garbo, MD | |
| A. O. Ospedale Civile di Vimercate | Recruiting |
| Vimercate, Italy | |
| Contact: Stefano Garducci, MD | |
| Principal Investigator: Stefano Garducci, MD | |
| Policlinico San Marco | Recruiting |
| Zingonia, Italy | |
| Contact: Nicoletta De Cesare, MD | |
| Principal Investigator: Nicoletta De Casare, MD | |
| Principal Investigator: | Marco Valgimigli, MD, PhD | University Hospital of Ferrara |
Publications:
| Responsible Party: | Italian Society of Invasive Cardiology |
| ClinicalTrials.gov Identifier: | NCT01477775 |
| Other Study ID Numbers: |
RFBU 13-I-PRU |
| First Posted: | November 23, 2011 Key Record Dates |
| Last Update Posted: | September 3, 2014 |
| Last Verified: | September 2014 |
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myocardial infarction coronary stent Oral P2Y12 receptor blocker Platelet reactivity units (PRU) |
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Acute Coronary Syndrome Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Clopidogrel Ticagrelor Prasugrel Hydrochloride |
Platelet Aggregation Inhibitors Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |