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

NCT01090336 | Unknown

• 2 other identifiers: PC01S-235/2009
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Patients With Acute Coronary Syndrome

Keywords

platelet aggregation inhibition; prasugrel; clopidogrel; ACS

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the rate of drug resistance at time of index intervention.

  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)

  Routinely, platelet aggregation is evaluated ideally daily up to 96 hours after index event.

Secondary Outcomes (1)

• 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.

Study Arms (2)

Clopidogrel group

At the discretion of the attending cardiologist patients are treated with clopidogrel (600mg loading and 75mg daily dose)

Prasugrel group

At the discretion of the attending cardiologist patients are treated with prasugrel (60mg loading and 10mg daily dose)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Patients with weight \< 60 kg, age \> 75 year or history of TIA, stroke or intracranial bleeding according to prasugrel contraindications
• 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

Sponsors & Collaborators

• Heidelberg University: lead
• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: collaborator

Study Sites (1)

University of Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 16423907 RESULT

Study Officials

• Evangelos Giannitsis, Prof. Dr.

  Department of Cardiology, University of Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: March 19, 2010
• Study Start: August 1, 2009
• Study Completion: December 1, 2011
• Last Updated: April 18, 2011

Record last verified: 2010-03

Locations

DE (1)