Biological Efficacy of Clopidogrel After Implantation of Drug-eluting Stents (SPACE) - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Collaborator:	Sanofi-Aventis
Information provided by (Responsible Party):	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00298428

Purpose

The risk of thrombotic complications after implantation of drug-eluting stents (DES) may be increased in patients with diabetes mellitus (DM) or metabolic syndrome (MS). It is recommended that all patients take an association of aspirin and clopidogrel for several months after DES implantation to reduce this risk. However, the biological efficacy of current antiplatelet therapies has not been studied prospectively and specifically in DM or MS patients.

Our aim is to study the biological efficacy of an association of aspirin and clopidogrel (600 mg loading dose followed by 75 mg maintenance dose) using an assay measuring ex vivo shear-induced platelet aggregation (SIPA), along with other assays measuring platelet activation and aggregation, in patients with DM, MS, or no DM/MS.

Patients with stable coronary artery disease and successful DES implantation in native coronary arteries will be eligible. They will be stratified at entry according to their metabolic status (DM, MS, or no DM/MS). Measurements will be performed 6-24 hours after clopidogrel loading dose (acute effects) and 4 months later under clopidogrel maintenance dose (chronic effects).

Study end-points:

A. Primary biological end-point: To compare SIPA levels in DM vs. MS vs. no DM/MS patients.

B. Secondary biological end-points:

To compare the results of other tests of platelet aggregation/activation in DM vs. MS vs. no DM/MS patients.
To compare the acute (6-24 hours after clopidogrel loading dose) and chronic (4 months later) results of the above mentioned tests. These comparisons will be performed in the overall population and in each group (DM, MS, no DM/MS).

C. Secondary clinical end-points: To study the relationship between SIPA levels (and the other tests of platelet aggregation/activation) and the occurrence of:

Periprocedural myocardial infarctions
Major adverse cardiac events (cardiovascular death, myocardial infarction or ischaemia-driven target vessel revascularization) at 4 and 12 months after stent implantation.

We, the researchers at Assistance PUBLIQUE - HOPITAUX de Paris, anticipate our study may help improve our knowledge of the efficacy of current antiplatelet therapies in DM and MS patients treated with DES.

Condition	Intervention
Coronary Artery Disease Atherosclerosis Diabetes Mellitus Metabolic Syndrome X	Procedure: blood samples

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Biological Efficacy of Clopidogrel 600 mg Loading Dose Followed by 75 mg Maintenance Dose After Implantation of Drug-eluting Stents in Patients With Diabetes Mellitus or Metabolic Syndrome (SPACE)

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Atherosclerosis Coronary Artery Disease Metabolic Syndrome

Drug Information available for: Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Primary biological end-point: To compare SIPA levels in DM vs. MS vs. no DM/MS patients [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment:	159
Study Start Date:	May 2006
Study Completion Date:	December 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
SPACE group	Procedure: blood samples blood samples before percutaneous coronary intervention (PCI) and at 4 months Other Name: blood samples before percutaneous coronary intervention

Detailed Description:

The risk of thrombotic complications after implantation of drug-eluting stents (DES) in coronary arteries may be increased in patients with diabetes mellitus (DM) or metabolic syndrome (MS). It is recommended that all patients take an association of aspirin and clopidogrel for several months after DES implantation to reduce this risk. However, the biological efficacy of current antiplatelet therapies has not been studied prospectively and specifically in DM or MS patients.

In the present study, we will study the biological efficacy of an association of aspirin and clopidogrel (600 mg loading dose followed by 75 mg maintenance dose) using an assay measuring ex vivo shear-induced platelet aggregation (SIPA), along with other assays measuring platelet activation and aggregation, in order to better describe the heterogeneity of response to antiplatelet agents in patients with DM, MS or no DM/MS.

All patients with stable coronary artery disease and successful DES implantation in native coronary arteries (including high risk features, eg, left main stenosis, bifurcations or in-stent restenosis) will be eligible. They will be stratified at entry according to their metabolic status (DM, MS, or no DM/MS). Measurements will be performed both 6-24 hours after clopidogrel loading dose (acute effects) and 4 months later under clopidogrel maintenance dose (chronic effects).

Study end-points:

A. Primary biological end-point: To compare SIPA levels in DM vs. MS vs. no DM/MS patients.

B. Secondary biological end-points:

To compare the results of other tests of platelet aggregation/activation (light transmittance aggregometry in response to ADP and arachidonic acid; flow cytometry measurements of VASP phosphorylation, platelet expression of P-selectin and GPIIbIIIa, and circulating levels of platelet microparticles and leukocyte-platelet aggregates; PFA-100 occlusion time; circulating levels of thromboxane B2) and circulating levels of other markers of atherosclerosis (CRPhs, von Willebrand factor, PAI-1, fibrinogen, and soluble CD40L) in DM vs. MS vs. no DM/MS patients.
To compare the acute (6-24 hours after clopidogrel loading dose) and chronic (4 months later) results of all the above mentioned tests. These comparisons will be performed in the overall population and in each group (DM, MS, no DM/MS).

C. Secondary clinical end-points: To study the relationship between SIPA levels (and the other tests of platelet aggregation/activation) and the occurrence of:

Periprocedural myocardial infarctions
Major adverse cardiac events (cardiovascular death, myocardial infarction or ischaemia-driven target vessel revascularization) at 4 and 12 months after stent implantation.

We anticipate our study may help improve our knowledge of the efficacy of current antiplatelet therapies in DM and MS patients treated with DES.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥18 years
Documented myocardial ischaemia (stable angina with positive stress ECG or stress myocardial scintigraphy, silent ischemia with positive stress ECG or stress myocardial scintigraphy, non-ST elevation acute coronary syndrome)
Treatment with at least 100 mg/day of aspirin for ≥ 6 hours before percutaneous coronary intervention
600 mg clopidogrel loading-dose given ≥ 6 hours and < 24 hours before coronary angiography
Presence of one or several stenosis in native coronary arteries requiring percutaneous coronary intervention and implantation of one or several drug-eluting stents

Exclusion Criteria:

ST-elevation acute coronary syndrome
Pregnancy or breast feeding
Severe disease with life expectancy lower than 1 year
High bleeding risk (blood coagulation disorders, uncontrolled severe hypertension, active bleeding, history of severe bleeding)
Intolerance or contraindication to aspirin or clopidogrel
Current treatment (or stopped < 10 days) with vitamin K antagonist
Current treatment (or stopped < 10 days) with clopidogrel (except for the clopidogrel loading-dose given prior to percutaneous coronary intervention), ticlopidine, dipyridamole, non-steroidal antiinflammatory agent, GPIIB-IIIA blocker
One-year follow-up impossible
Refusal to sign the information and consent form

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00298428

Locations

France
Département de Cardiologie, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris
Paris, France, 75018
Service d'Hématologie et d'Immunologie Biologiques, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris
Paris, France, 75018

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Sanofi-Aventis

Investigators

Principal Investigator:	Laurent J Feldman, MD, PhD	Département de Cardiologie, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris
Principal Investigator:	Nadine Ajzenberg, MD, PhD	Service d'Hématologie et d'Immunologie Biologiques, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris

More Information

Publications:

Silber S, Albertsson P, Aviles FF, Camici PG, Colombo A, Hamm C, Jorgensen E, Marco J, Nordrehaug JE, Ruzyllo W, Urban P, Stone GW, Wijns W; Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J. 2005 Apr;26(8):804-47. Epub 2005 Mar 15.

Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005 Jan 18;45(2):246-51.

Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003 Jun 17;107(23):2908-13. Epub 2003 Jun 9.

Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schomig A; Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Study Investigators. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004 Jan 15;350(3):232-8.

Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation. 2005 Apr 26;111(16):2099-106. Epub 2005 Mar 6.

Matetzky S, Shenkman B, Guetta V, Shechter M, Bienart R, Goldenberg I, Novikov I, Pres H, Savion N, Varon D, Hod H. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004 Jun 29;109(25):3171-5. Epub 2004 Jun 7.

Ajzenberg N, Aubry P, Huisse MG, Cachier A, El Amara W, Feldman LJ, Himbert D, Baruch D, Guillin MC, Steg PG. Enhanced shear-induced platelet aggregation in patients who experience subacute stent thrombosis: a case-control study. J Am Coll Cardiol. 2005 Jun 7;45(11):1753-6.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00298428 History of Changes
Other Study ID Numbers:	P051004
Study First Received:	March 1, 2006
Last Updated:	September 23, 2011
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Assistance Publique - Hôpitaux de Paris:

stent
percutaneous coronary intervention
platelet aggregation

clopidogrel
shear
metabolic syndrome

Additional relevant MeSH terms:

Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Metabolic Syndrome X
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Insulin Resistance
Hyperinsulinism
Clopidogrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012