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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00298428
First received: March 1, 2006
Last updated: September 23, 2011
Last verified: June 2011
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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:

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 - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:
stent
percutaneous coronary intervention
platelet aggregation
clopidogrel
shear
metabolic syndrome

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Coronary Artery Disease
Coronary Disease
Diabetes Mellitus
Metabolic Syndrome X
Myocardial Ischemia
Syndrome
Arterial Occlusive Diseases
Cardiovascular Diseases
Disease
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Hyperinsulinism
Insulin Resistance
Metabolic Diseases
Pathologic Processes
Vascular Diseases
Clopidogrel
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists

ClinicalTrials.gov processed this record on October 22, 2014