Clinical trial NCT01090336: Prasugrel Versus Clopidogrel in Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI)
Official title: Prevalence of Inadequate Platelet Inhibition After Oral Loading With Prasugrel/Clopidogrel in Patients With an Acute Coronary Syndrome Undergoing Early PCI
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Patients With Acute Coronary Syndrome
Keywords: platelet aggregation inhibition
prasugrel
clopidogrel
ACS
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
First posted: 2010-03-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population includes 80 subjects with moderate to high-risk ACS, ie patients with unstable angina (UA) and non-ST-segment elevation MI (NSTEMI) and TIMI risk score of 3 or higher, within 72 hours after onset of symptoms. In all patients early PCI is planned. Patients with exclusion criteria for prasugrel will be excluded for clopidogrel as well.

Brief summary: Background: Both prasugrel and clopidogrel are prescribed drugs which compete as platelet inhibitors in patients with acute coronary syndrome (ACS). Whether rates of drug resistance/hyporesponsiveness are lower with prasugrel and whether more consistent and earlier onset of platelet inhibition may reduce infarct size in patients with ACS undergoing early PCI remains, at present, unknown.

Study design/study population: This trial is a prospective, open-label, single centre observational trial. Patients receive either prasugrel (60mg) or clopidogrel (600mg) at the discretion of the attending cardiologist. Patients with exclusion criteria for prasugrel will be excluded for clopidogrel as well. The study population includes 80 subjects with moderate to high-risk ACS, ie patients with unstable angina (UA) and non-ST-segment elevation MI (NSTEMI) and TIMI risk score of 3 or higher, within 72 hours after onset of symptoms. In all patients early PCI is planned.

Study objective/endpoint/methods: The primary objective of this trial is to evaluate whether rates of hyporesponsiveness are lower with prasugrel and whether more consistent and earlier onset of platelet inhibition may reduce infarct size in ACS in patients undergoing early PCI.

The primary endpoint is the rate of drug resistance at time of index intervention. Optical and impedance aggregometry using ADP (5 and 20 μM) and collagen (1 μg/ml) as platelet agonists is used to measure platelet aggregation. Addition of the specific antagonists aspirin and mesamp to the probe is used to discriminate between pharmacodynamic and pharmacokinetic drug resistance.

Secondary endpoint is the reduction of myocardial infarct size determined by post-interventional increase of high sensitive TnT (TnT hs) during the days following the index event reflecting earlier, more effective and more consistent inhibition of platelet function.

Tertiary endpoint is the composite clinical endpoint of cardiovascular death, nonfatal MI, or stroke and urgent target vessel revascularization during hospitalization and after 6 and 12 months.

Safety endpoint is any TIMI major or minor bleeding during hospital stay and after 6 and 12 months including intracranial and life-threatening bleeding.

Detailed description: look above

Eligibility criteria: Inclusion criteria:

* Patients with unstable angina or non-ST-elevation myocardial infarction with ischemic symptoms lasting 10 minutes or more and occurring within 72 hours before randomization,
* A TIMI risk score of 3 or more, and
* Either ST-segment deviation of 1 mm or more or elevated levels of a cardiac biomarker of necrosis.
* Legal age (and ≥18 y) and competent mental condition to provide written informed consent

Exclusion Criteria:

* Patients with weight \< 60 kg, age \> 75 year or history of TIA, stroke or intracranial bleeding according to prasugrel contraindications
* Clinical status forbid inclusion (eg cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, New York Heart Association class IV congestive heart failure etc)
* Bleeding risk exclusion criteria including fibrin-specific and non-fibrin-specific fibrinolytic therapy for index event, active internal bleeding or history of bleeding diathesis or any clinical findings in the judgment of the investigator associated with an increased risk of bleeding
* History of hemorrhagic stroke, intracranial neoplasm, arteriovenous malformation, or aneurysm
* Ischemic stroke within 3 months prior to screening
* Oral anticoagulation or INR greater than 1.5 at the time of screening
* Platelet count of less than 100 000/mm3 at the time of screening
* Anemia (hemoglobin \<10 g/dL) at the time of screening
* Prior/concomitant therapy with thienopyridine or daily treatment with nonsteroidal antiinflammatory drugs or cyclooxygenase-2 inhibitors
* General exclusion criteria

Primary outcomes:
measure: The primary endpoint is the rate of drug resistance at time of index intervention.
timeFrame: Routinely, platelet aggregation is evaluated ideally daily up to 96 hours after index event.
Secondary outcomes:
measure: Secondary endpoint is the reduction of myocardial infarct size determined by post-interventional increase of high sensitive TnT (TnT hs).
timeFrame: Routinely, ideally daily until 96h after index event.
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University of Heidelberg
state: Baden-Württemberg
Study officials:
affiliation: Department of Cardiology, University of Heidelberg
name: Evangelos Giannitsis, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ivandic BT, Schlick P, Staritz P, Kurz K, Katus HA, Giannitsis E. Determination of clopidogrel resistance by whole blood platelet aggregometry and inhibitors of the P2Y12 receptor. Clin Chem. 2006 Mar;52(3):383-8. doi: 10.1373/clinchem.2005.059535. Epub 2006 Jan 19.