Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.

Atherosclerosis Clinical Trial

— ASCET  

Official title:

Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00222261
• Other study ID #: ASCET
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: March 22, 2011
• Start date: April 2003
• Est. completion date: July 2010

Study information

• Verified date: March 2011
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research EthicsNorway: Norwegian Medicines AgencyNorway: The Data Inspectorate
• Study type: Interventional

Clinical Trial Summary

In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75mg/d. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response, assessed by the PFA-100® method, to investigate whether aspirin non-responders have higher composite event rate than responders or whether Clopidogrel treatment in patients non-responsive to aspirin will reduce their risk of future clinical events. The clinical events are the composite of unstable angina, myocardial infarction, stroke or death.

Description:

Background: Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease. Despite documented clinical benefit, many patients on aspirin still experience severe cardiovascular events. Several laboratory reports have shown lack of platelet inhibition in 5-40% of aspirin-treated patients, and the term aspirin resistance has been introduced. The clinical relevance of these laboratory findings is, however, still unknown. New antiplatelet drugs have been developed, and the adenosin diphosphate (ADP) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile. Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming. New methodologies, like the PFA-100® system, have made such analyses more suitable for clinical use.

Design: In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75mg/d after initial determination of their platelet reactivity while on aspirin treatment. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response.

Scand Cardiovasc J. 2004 Dec;38(6):353-6.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1001
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Stable, symptomatic coronary heart disease, verified by coronary angiography, being treated with angioplasty/stent implantation (PCI) or not.

Exclusion Criteria:

• Indication for warfarin treatment.

• Indication for or contraindication to the study drugs.

• Pregnancy or breast-feeding.

• Malignancy that may interfere with life expectancy.

• Psychiatric disease, mental retardation, dementia, drug abuse, alcoholism or conditions that can severely reduce compliance.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• aspirin
Aspirin 160 mg once daily for two years
• clopidogrel
clopidogrel 75 mg once daily for two years

Locations

Country	Name	City	State
Norway	Ullevaal University Hospital	Oslo

Sponsors (5)

Lead Sponsor	Collaborator
Ullevaal University Hospital	Ada and Hagbart Waages Humanitarian and Charity Foundation, Alf and Aagot Helgesens Research Foundation., The Norwegian Council for Cardiovascular Diseases., The Scientific Board, Ullevål University Hospital.

Country where clinical trial is conducted

Norway, 

References & Publications (15)

Andersen K, Hurlen M, Arnesen H, Seljeflot I. Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease. Thromb Res. 2002 Oct 1;108(1):37-42. — View Citation

Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. Erratum in: BMJ 2002 Jan 19;324(7330):141. — View Citation

Buchanan MR, Brister SJ. Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol. 1995 Mar;11(3):221-7. — View Citation

Buchanan MR, Schwartz L, Bourassa M, Brister SJ, Peniston CM; BRAT Investigators. Results of the BRAT study--a pilot study investigating the possible significance of ASA nonresponsiveness on the benefits and risks of ASA on thrombosis in patients undergoing coronary artery bypass surgery. Can J Cardiol. 2000 Nov;16(11):1385-90. — View Citation

CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. — View Citation

De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregation tests? J Thromb Haemost. 2003 Sep;1(9):2048-50. — View Citation

Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res. 1993 Sep 1;71(5):397-403. — View Citation

Grotemeyer KH. Effects of acetylsalicylic acid in stroke patients. Evidence of nonresponders in a subpopulation of treated patients. Thromb Res. 1991 Sep 15;63(6):587-93. — View Citation

Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, Sapp SK, Topol EJ. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol. 2001 Aug 1;88(3):230-5. — View Citation

Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003 Mar 19;41(6):961-5. Erratum in: J Am Coll Cardiol. 2006 Nov 7;48(9):1918. — View Citation

Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD. Development of aspirin resistance in persons with previous ischemic stroke. Stroke. 1994 Dec;25(12):2331-6. — View Citation

Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-74. — View Citation

Hurlen M, Seljeflot I, Arnesen H. The effect of different antithrombotic regimens on platelet aggregation after myocardial infarction. Scand Cardiovasc J. 1998;32(4):233-7. — View Citation

Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. Review. — View Citation

Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H. Unstable angina, stroke, myocardial infarction and death in aspirin non-responders. A prospective, randomized trial. The ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint Trial) design. Scand Cardiovasc J. 2004 Dec;38(6):353-6. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality		2 years	No
Primary	Myocardial infarction		2 years	No
Primary	Unstable angina with ECG changes or raised levels of cardiac markers not to be classified as a myocardial infarction		2 years	No
Secondary	Instent restenosis and/or thrombosis detected by coronary angiography.		2 years	No