Dual Antiplatelet Therapy Tailored on the Extent of Platelet Inhibition

Unstable Angina Clinical Trial

— DANTE  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00774475
• Other study ID #: 000
• Status: Not yet recruiting
• Phase: Phase 3
• First received: October 16, 2008
• Last updated: October 23, 2008
• Start date: November 2008
• Est. completion date: January 2011

Study information

• Verified date: October 2008
• Source: University of Florence
• Contact: Gian Franco Gensini, MD
• Phone: 00390557949417
• Email: g.gensini[@]dac.unifi.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 442
• Est. completion date: January 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 90 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina, Unstable
• NSTEMI
• Unstable Angina

Intervention

Drug:
• comparison of different dosage of clopidogrel
clopidogrel 75 mg/day versus clopidogrel 150 mg/day
• doubled therapy
clopidogrel 150 mg/day

Locations

Country	Name	City	State
Italy	University of Florence	Florence

Sponsors (2)

Lead Sponsor	Collaborator
University of Florence	Tuscany Region

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View 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. Epub 2007 Jun 4. — View 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. — View 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. — View 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. Epub 2006 Sep 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of MACE (cardiovascular death, nonfatal myocardial infarction, target lesion vessel revascularization by PCI or coronary bypass)		6 and 12 months	Yes
Secondary	Stent thrombosis with angiographic confirmation; platelet function assessed by VerifyNow P2Y12 1 week after the randomization		1 week; 6 and 12 months	No