Dual Antiplatelet Therapy Tailored on the Extent of Platelet Inhibition (DANTE)

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

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).

Study Overview

• Status: Unknown
• Conditions: Unstable Angina; NSTEMI
• Intervention / Treatment: Drug: comparison of different dosage of clopidogrel; Drug: doubled therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 442
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50134
    • University of Florence

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1: standard therapy; clopidogrel 75 mg/day	Drug: comparison of different dosage of clopidogrel; clopidogrel 75 mg/day versus clopidogrel 150 mg/day
Active Comparator: 2: doubled therapy; clopidogrel 150 mg/day	Drug: doubled therapy; clopidogrel 150 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of MACE (cardiovascular death, nonfatal myocardial infarction, target lesion vessel revascularization by PCI or coronary bypass)	6 and 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Stent thrombosis with angiographic confirmation; platelet function assessed by VerifyNow P2Y12 1 week after the randomization	1 week; 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Tuscany Region
• Investigators: Principal Investigator: Gian Franco Gensini, MD, University of Florence; Study Chair: Gianni Maria Santoro, MD, ASL 10 Florence, Italy; Study Chair: Niccolò Marchionni, MD, University of Florence; Study Chair: David Antoniucci, MD, Azienda Ospedaliero-Universitaria Careggi; Study Chair: Alfredo Zuppiroli, MD, ASL 10 Florence Italy; Study Chair: Maria Cristina Landini, MD, ASL 10 Florence Italy; Study Director: Rosanna Abbate, MD, University of Florence

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Anticipated): November 1, 2010
• Study Completion (Anticipated): January 1, 2011

Study Registration Dates

• First Submitted: October 16, 2008
• First Submitted That Met QC Criteria: October 16, 2008
• First Posted (Estimate): October 17, 2008

Study Record Updates

• Last Update Posted (Estimate): October 24, 2008
• Last Update Submitted That Met QC Criteria: October 23, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Clopidogrel therapy; platelet function inhibition
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: 000 (Other Identifier: CTGTY)