Clinical trial NCT00352014: Evaluation and Comparison of Several Point-of-care Platelet Function Tests in Predicting Clinical Outcomes in Clopidogrel Pre-treated Patients Undergoing Elective PCI.
Official title: Do Point-of-care Platelet Function Assays Predict Clinical Outcomes in Clopidogrel Pre-treated Patients Undergoing Elective PCI. (The POPular Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stable Angina Pectoris
Keywords: Monitoring of antiplatelet therapy
antiplatelet therapy
platelet function assays
Aspirin
Clopidogrel
elective PCI
Lead sponsor: R&D Cardiologie
Sponsor class: OTHER
First posted: 2006-07-14
Enrollment: 1000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: The purpose of this study is to investigate whether the level of Platelet Inhibition as assessed with five point-of-care platelet function assays correlates with clinical (periprocedural) outcomes such as Acute Myocardial Infarction, death, Target Vessel revascularization and/or stroke in patients undergoing elective PCI.

Detailed description: Antiplatelet agents-aspirin, thienopyridines, and platelet glycoprotein IIb/IIIa (GpIIb/IIIa) inhibitors-have become cornerstones in the treatment of ischemic heart disease for patients undergoing percutaneous coronary intervention (PCI)1,2. However, several studies have demonstrated with the use of platelet function assays that subgroups of patients receiving either aspirin, clopidogrel, or both fail to produce the anticipated antiplatelet effect3-5. Consequently, terms like "aspirin-resistance" and "clopidogrel resistance" have been introduced in literature.

Light transmittance platelet aggregometry is generally considered to be the gold standard for determining platelet function, but its relevance to in vivo platelet function is questionable and the logistically demands of the method make it impossible to use in daily practice. In addition, aggregation is just one of several important platelet functions. The introduction of several point-of-care assays may be the key to the widespread clinical use of platelet function testing to identify so called anti-platelet therapy low-responders. However, whether these point-of-care platelet function tests provide predictive value (i.e. correlate with clinical outcomes) and the allocation of the "best" or most suitable point-of-care Platelet function assay to determine the level of inhibition of platelet function remains to be established.

Eligibility criteria: Inclusion Criteria:

* Coronary artery disease with objective evidence of ischemia (e.g., symptoms of angina pectoris, positive results of a stress test or dynamic electrocardiographic \[ECG\] changes)
* Adequate Aspirin and Clopidogrel pre-treatment.( Adequate clopidogrel pre-treatment is defined as a 600 mg loading dose of clopidogrel at least 6 hours prior to the PCI-procedure or a 300 mg loading dose of clopidogrel \>24 hours prior to the PCI-procedure or a 75 mg dose of clopidogrel for at least \>5 days prior to the PCI procedure
* Patient is thought to be at a high likelihood for requiring PCI (significant angiographic lesions in native coronary arteries amenable to and requiring a percutaneous coronary intervention)
* A stent (either drug-eluting or bare metal) is planned to be placed in at least one lesion.
* Written Informed consent

Exclusion Criteria:

* ST-segment elevation Acute Myocardial Infarction (ST-segment ≥0.1mV in ≥2 contiguous ECG leads persisting for at least 20 minutes) within 48 hours from symptom onset.
* Contraindications to antithrombotic/antiplatelet therapy
* Failed coronary intervention in the previous 2 weeks
* Malignancies
* Increased risk of bleeding (previous stroke in the past months, active bleeding or bleeding diathesis, recent trauma or major surgery in the last month, suspected aortic dissection, oral anticoagulation therapy with coumarin derivate within 7 days, recent use of GPIIb/IIIa inhibitors within 14 days, severe uncontrolled hypertension \>180 mmHg unresponsive to therapy)
* Relevant hematologic deviations (hemoglobin \<100g/L (6,2 mmol/L) or hematocrit \<34%, platelet count \<100 x 109 /L or platelet count \> 600 x 109/L)
* Known allergy to clopidogrel
* Pregnancy (present or suspected)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: Department of Cardiology, St. Antonius Hospital, The Netherlands
state: Utrecht
Study officials:
affiliation: Department of Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands
name: Jurrien M ten Berg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Research and Development in Cardiology, St. Antonius Hospital Nieuwegein, The Netherlands
name: Jochem W van Werkum, MD
role: STUDY_CHAIR
affiliation: Department of Clinical Chemistry, Nieuwegein, St. Antonius Hospital The Netherlands
name: Christian M Hackeng, PhD
role: STUDY_CHAIR
References:
citation: Bouman HJ, Harmsze AM, van Werkum JW, Breet NJ, Bergmeijer TO, Ten Cate H, Hackeng CM, Deneer VH, Ten Berg JM. Variability in on-treatment platelet reactivity explained by CYP2C19*2 genotype is modest in clopidogrel pretreated patients undergoing coronary stenting. Heart. 2011 Aug;97(15):1239-44. doi: 10.1136/hrt.2010.220509. Epub 2011 May 31.
citation: Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Harmsze AM, Hackeng CM, ten Berg JM. High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention. Heart. 2011 Jun;97(12):983-90. doi: 10.1136/hrt.2010.220491. Epub 2011 Apr 8.
citation: Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010 Feb 24;303(8):754-62. doi: 10.1001/jama.2010.181.