Clinical trial NCT00774475: Dual Antiplatelet Therapy Tailored on the Extent of Platelet Inhibition
Official title: Optimization of Antiplatelet Therapy With Clopidogrel on the Basis of the Extent of Platelet Inhibition in Patients With Acute Coronary Syndromes on Dual Antiplatelet Therapy Undergoing PCI With Stent Implantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Unstable Angina
NSTEMI
Keywords: Clopidogrel therapy
platelet function inhibition
Lead sponsor: University of Florence
Sponsor class: OTHER
Collaborators: name: Tuscany Region
First posted: 2008-10-17
Enrollment: 442
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy (reduction of major ischemic events at 6 and 12 months of follow-up) of a tailored clopidogrel therapy in patients with UA/NSTEMI undergoing PCI with stent implantation and wiht a documented residual platelet reactivity assessed by a point of care system (VerifyNow P2Y12).

Detailed description: Several studies documented the presence of a high variability in the individual response to antiplatelet therapies in terms of extent of platelet function inhibition. This laboratory finding is the so-called aspirin or clopidogrel resistance which we prefer to define residual platelet reactivity (RPR) on antiplatelet therapy.

A growing body of evidence is demonstrating the clinical relevance of this laboratory parameter, i.e. patients with RPR are at higher risk of a subsequent adverse cardiovascular event.

In particular, it has been demonstrated that RPR measured by light transmittance aggregometry induced by ADP or by the point of care assay VerifyNow P2Y12 identifies patients which, after coronary revascularization with stent implantation, at higher risk of a potentially catastrophic event such as stent thrombosis.

No randomized trials are available in the literature on the efficacy and safety of an antiplatelet therapy tailored on the extent of platelet function inhibition.

Eligibility criteria: Inclusion Criteria:

* Unstable or NSTEMI

Exclusion Criteria:

Previous bleeding events which have required blood transfusion

* PT- INR \>1.5
* Platelet count ≤ 100000/ mm3
* Hb \< 10 g/dl
* Previous TIA/stroke (ischemic or hemorrhagic or unknown)
* Body weight \< 60 Kg
* Creatinine levels ≥ 4 mg/dl
* Cerebral neoplasia
* Recent major trauma/surgery/head injury (within 3 previous weeks)
* Gastrointestinal hemorrhage in the last month
* Aortic dissection
* Known haemorrhagic diathesis
* Oral anticoagulant therapy
* Pregnancy or 1 week after delivery
* Uncontrolled hypertension (systolic \>180 mmHg or diastolic \>110 mmHg)
* Severe liver disease
* Infective endocarditis
* Major psychiatric disorders
* Alcool or drug abuse
* Active peptic ulcer Noncompressible arterial puncture within 14 days Prolonged cardiopulmonary resuscitation

Primary outcomes:
measure: Incidence of MACE (cardiovascular death, nonfatal myocardial infarction, target lesion vessel revascularization by PCI or coronary bypass)
timeFrame: 6 and 12 months
Secondary outcomes:
measure: Stent thrombosis with angiographic confirmation; platelet function assessed by VerifyNow P2Y12 1 week after the randomization
timeFrame: 1 week; 6 and 12 months
Other outcomes:
Locations:
city: Florence
country: Italy
facility: University of Florence
Study officials:
affiliation: University of Florence
name: Gian Franco Gensini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ASL 10 Florence, Italy
name: Gianni Maria Santoro, MD
role: STUDY_CHAIR
affiliation: University of Florence
name: Niccolò Marchionni, MD
role: STUDY_CHAIR
affiliation: Azienda Ospedaliero-Universitaria Careggi
name: David Antoniucci, MD
role: STUDY_CHAIR
affiliation: ASL 10 Florence Italy
name: Alfredo Zuppiroli, MD
role: STUDY_CHAIR
affiliation: ASL 10 Florence Italy
name: Maria Cristina Landini, MD
role: STUDY_CHAIR
affiliation: University of Florence
name: Rosanna Abbate, MD
role: STUDY_DIRECTOR
References:
citation: Gori AM, Marcucci R, Migliorini A, Valenti R, Moschi G, Paniccia R, Buonamici P, Gensini GF, Vergara R, Abbate R, Antoniucci D. Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J Am Coll Cardiol. 2008 Aug 26;52(9):734-9. doi: 10.1016/j.jacc.2008.05.032.
citation: Buonamici P, Marcucci R, Migliorini A, Gensini GF, Santini A, Paniccia R, Moschi G, Gori AM, Abbate R, Antoniucci D. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007 Jun 19;49(24):2312-7. doi: 10.1016/j.jacc.2007.01.094. Epub 2007 Jun 4.
citation: Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, Ernst A, Sawhney NS, Schatz RA, Teirstein PS. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008 Apr;29(8):992-1000. doi: 10.1093/eurheartj/ehn046. Epub 2008 Feb 10.
citation: Santoro GM, Carrabba N, Barchielli A, Balzi D, Marchionni N, Filice M, Valente S, Granelli M, Berni I, Buiatti E; AMI-Florence Working Group. Use and efficacy of abciximab in an unselected population with acute myocardial infarction treated with primary angioplasty: data from AMI-Florence registry. Atherosclerosis. 2007 Nov;195(1):116-21. doi: 10.1016/j.atherosclerosis.2006.08.053. Epub 2006 Sep 25.
citation: Balzi D, Barchielli A, Buiatti E, Franceschini C, Lavecchia R, Monami M, Santoro GM, Carrabba N, Margheri M, Olivotto I, Gensini GF, Marchionni N; AMI-Florence Working Group. Effect of comorbidity on coronary reperfusion strategy and long-term mortality after acute myocardial infarction. Am Heart J. 2006 May;151(5):1094-1100. doi: 10.1016/j.ahj.2005.06.037.