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

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Unstable Angina
• Intervention / Treatment: Drug: Prasugrel; Drug: Clopidogrel

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 50937
    • Cardiology, University Hospital of Cologne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel; 3 months treatment with 10 mg prasugrel	Drug: Prasugrel; 3 months treatment; Other Names: Efient
Active Comparator: Clopidogrel; 3 months treatment with clopidogrel 75 mg	Drug: Clopidogrel; 3 months treatment; Other Names: Plavix

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Cologne
• Investigators: Principal Investigator: Tanja Rudolph, MD, University Hospital of Cologne

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: January 16, 2013
• First Submitted That Met QC Criteria: January 21, 2013
• First Posted (Estimate): January 24, 2013

Study Record Updates

• Last Update Posted (Estimate): June 11, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Disease; Chest Pain; Angina Pectoris; Syndrome; Acute Coronary Syndrome; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: Uni-Koeln-1649