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

September 23, 2011 updated by: Assistance Publique - Hôpitaux de Paris

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

159

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75018
        • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: SPACE group
Procedure: blood samples
blood samples before percutaneous coronary intervention (PCI) and at 4 months
Other Names:
  • blood samples before percutaneous coronary intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Primary biological end-point: To compare SIPA levels in DM vs. MS vs. no DM/MS patients
Time Frame: 4 months
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

March 1, 2006

First Submitted That Met QC Criteria

March 1, 2006

First Posted (Estimate)

March 2, 2006

Study Record Updates

Last Update Posted (Estimate)

September 26, 2011

Last Update Submitted That Met QC Criteria

September 23, 2011

Last Verified

June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P051004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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