Vasoactive and Anti-inflammatory Effects of Prasugrel in Acute Coronary Syndrome

Study Overview
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Brief Summary
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To test the vasoactive and anti-inflammatory effects of prasugrel in patients with acute coronary syndrome endothelial function -as a surrogate parameter of NO bioavailability- and different markers of inflammation, oxidative stress and platelet activation will be assessed in patients with unstable angina.

Detailed Description
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Trial Objectives To test the vasoactive and anti-inflammatory effects of prasugrel in patients with acute coronary syndrome, endothelial function -as a surrogate parameter of NO bioavailability- and different markers of inflammation, oxidative stress and platelet activation will be assessed in patients with unstable angina. Trial Design Single center, double blind, double-dummy, randomized, parallel trial. Endpoints Primary Endpoint Assessment of endothelial function (FMD) via high-resolution ultrasound (Sonoline G50, 12 MHz linear array transducer, Siemens, Germany) by experienced sonographer. Secondary Endpoints Non-invasive assessment of microvascular perfusion and oxygen saturation by laser Doppler perfusion imaging and tissue spectrometry (O2C, Lea Medizintechnik, Giessen, Germany) Determination of leukocyte activity: plasma MPO levels (ELISA), plasma elastase levels (ELISA) Assessment of platelet activity: plasma levels of sCD40 ligand (ELISA), RANTES (ELISA) Measurement of different oxidative stress markers: hsCRP (ELISA), CD40 ligand (ELISA), carbonylated proteins (ELISA), urinary 8-iso-PGF2α (gas chromatography mass spectrometry) Determination of platelet-leukocyte aggregates by fluorescent activated cell sorter (FACS) Assessment of platelet function (PADA-test)

Official Title
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Vasoactive and Anti-inflammatory Effects of Prasugrel in Acute Coronary Syndrome

Conditions
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Acute Coronary Syndrome, Unstable Angina

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute coronary syndrome, unstable angina planned percutaneous coronary intervention Written informed consent Exclusion Criteria: - Age < 18 years or ≥75 years Body weight < 60 kg STEMI, NSTEMI Cardiogenic shock at the time of randomization Refractory ventricular arrhythmias Congestive heart failure (NYHA IV) Increased risk of bleeding Active internal bleeding or history of hemorrhagic diathesis History of TIA, ischemic or hemorrhagic stroke Intracranial neoplasm, aneurysm and arteriovenous malformation INR > 1.5 at screening Platelets < 100,000/ml Anemia (Hb < 10 g/dl) at screening One or more doses of a thienopyridine 5 d or less before PCI Oral anticoagulation which cannot be safely discontinued for the duration of the study One or more doses of a thienopyridine 5 d or less before PCI Treatment within the last 30 d with an investigational drug or are presently enrolled in another drug or device study Women who are known to be pregnant, have given birth within the past 90 d, or are breast-feeding Concomitant medical illness that in the opinion of the investigator is associated with reduced survival over the expected treatment period Known severe hepatic dysfunction Any condition associated with poor treatment compliance, including alcoholism, mental illness, or drug dependence Intolerance of or allergy to aspirin, ticlopidine, or clopidogrel

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prasugrel<br>3 months treatment with 10 mg prasugrel | Drug: Prasugrel<br>* 3 months treatment<br>* Other names: Efient;|
| Active Comparator: Clopidogrel<br>3 months treatment with clopidogrel 75 mg | Drug: Clopidogrel<br>* 3 months treatment<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of endothelial function (FMD) via high-resolution ultrasound (Sonoline G50, 12 MHz linear array transducer, Siemens, Germany) by experienced sonographer | The primary endpoint is the change of endothelial function given in % from baseline to 3 months after therapy with prasugrel versus clopidogrel. | baseline and after 3 months |