Prasugrel Versus Clopidogrel in Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI)

• Conditions: Patients With Acute Coronary Syndrome

• Registration Number: NCT01090336
• Lead Sponsor: Heidelberg University

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

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Study Timeline

• Study Start: 2009-08
• Status Verified: 2010-03
• Study First Submitted: 2010-03-16
• Study First Submitted QC: 2010-03-18
• Study First Posted: 2010-03-19
• Last Update Submitted: 2011-04-15
• Last Update Posted: 2011-04-18
• Study Completion: 2011-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the rate of drug resistance at time of index intervention.	Routinely, platelet aggregation is evaluated ideally daily up to 96 hours after index event.	Platelet aggregation is determined by light transmission and impedance aggregometry as previoulsy described (Boris T. Ivandic, Philipp Schlick, Peter Staritz, Kerstin Kurz, Hugo A. Katus and Evangelos Giannitsis: Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor; Clinical Chemistry 52: 383-388, 2006)

Secondary Outcome Measures

Name	Time	Method
Secondary endpoint is the reduction of myocardial infarct size determined by post-interventional increase of high sensitive TnT (TnT hs).	Routinely, ideally daily until 96h after index event.

Trial Locations

Locations (1)

University of Heidelberg; 🇩🇪 Heidelberg, Baden-Württemberg, Germany