75 or 150 mg Clopidogrel Maintenance Doses Following PCI (ISAR-CHOICE-2)

Coronary Disease Clinical Trial

Official title:

A Double-Blind, Randomized Comparison Between Two Different Clopidogrel Maintenance Doses After Percutaneous Coronary Intervention (ISAR-CHOICE-2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140465
• Other study ID #: GE IDE No. A00803
• Status: Completed
• Phase: Phase 4
• First received: August 31, 2005
• Last updated: November 13, 2007
• Start date: October 2004
• Est. completion date: July 2005

Study information

• Verified date: November 2007
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to test whether an increase of the maintenance dose of clopidogrel from 75 to 150 mg per day results in an additional suppression of ADP-induced platelet aggregation

Description:

In patients treated with coronary stents clopidogrel therapy is usually initiated with a 300 to 600 mg loading dose. In the CREDO trial it was shown that a 300 mg loading dose results in a reduction of ischemic events after percutaneous coronary intervention (PCI) if given 6 hours prior to the procedure. An antiplatelet effect similar to that achieved by chronic therapy with 75 mg/day is reached within 2 hours when the high 600 mg loading is administered. The 600 mg loading dose has been shown to be safe and effective in preventing thrombotic events following coronary stent implantation. Recently, it was shown that in patients with stable angina and administration of the 600 mg loading dose at least two hours prior to PCI concomitant therapy with a GP IIb/IIIa antagonist does not result in a further reduction of the incidence of thrombotic events. In contrast to a number of investigations with different loading doses, no trials have been performed comparing different clopidogrel maintenance doses. Recently, it was shown that administration of a 600 mg loading dose in patients already on chronic clopidogrel therapy (75 mg/day) results in an additional significant increase in inhibition of adenosine diphosphate (ADP-) induced platelet aggregation. Therefore, it is possible that an increase of the clopidogrel maintenance dose in patients with chronic clopidogrel therapy also results in a more pronounced inhibition of platelet aggregation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with chronic aspirin therapy who are treated with percutaneous coronary intervention at least 2 hours after administration of a 600 mg loading dose of clopidogrel

Exclusion Criteria:

• Major alterations of blood count (particularly platelet count < 100x10^9/l, haemoglobin < 10 mg/dl

• Recent bleeding diathesis

• Presence of a hematologic or malignant disorder

• Oral anticoagulation with coumarin derivates

• Use of glycoprotein (GP) IIb/IIIa antagonists during the intervention or during the preceding 14 days

• Therapy with clopidogrel within the last 28 days

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease

Intervention

Drug:
• Clopidogrel
after PCI
• Clopidogrel
after PCI

Locations

Country	Name	City	State
Germany	Deutsches Herzzentrum Muenchen	Munich

Sponsors (2)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen	Technische Universität München

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC Jr; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation. 2002 Oct 1;106(14):1893-900. — View Citation

Gorchakova O, von Beckerath N, Gawaz M, Mocz A, Joost A, Schömig A, Kastrati A. Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting. Eur Heart J. 2004 Nov;25(21):1898-902. — View Citation

Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schömig A; Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Study Investigators. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004 Jan 15;350(3):232-8. — View Citation

Kastrati A, von Beckerath N, Joost A, Pogatsa-Murray G, Gorchakova O, Schömig A. Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation. 2004 Oct 5;110(14):1916-9. Epub 2004 Jul 19. — View Citation

Müller I, Seyfarth M, Rüdiger S, Wolf B, Pogatsa-Murray G, Schömig A, Gawaz M. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart. 2001 Jan;85(1):92-3. — View Citation

Pache J, Kastrati A, Mehilli J, Gawaz M, Neumann FJ, Seyfarth M, Hall D, Braun S, Dirschinger J, Schömig A. Clopidogrel therapy in patients undergoing coronary stenting: value of a high-loading-dose regimen. Catheter Cardiovasc Interv. 2002 Apr;55(4):436-41. — View Citation

Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ; CREDO Investigators. Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 Nov 20;288(19):2411-20. Erratum in: JAMA. 2003 Feb 26;289(8):987.. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal ADP(5µmol/l)-induced platelet aggregation 30 days after the intervention		30 days after the intervention
Secondary	Maximal ADP(20µmol/l)-induced platelet aggregation 30 days after the intervention		30 days after the intervention
Secondary	P2Y12 inhibition measured by point-of-care test		P2Y12 inhibition measured by point-of-care test