Aspirin Non-Responsiveness and Clopidogrel Endpoint Trial. - Full Text View

Sponsor:	Ullevaal University Hospital
Collaborators:	The Norwegian Council for Cardiovascular Diseases. The Scientific Board, Ullevål University Hospital. Ada and Hagbart Waages Humanitarian and Charity Foundation Alf and Aagot Helgesens Research Foundation.
Information provided by:	Ullevaal University Hospital
ClinicalTrials.gov Identifier:	NCT00222261

Purpose

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.

Condition	Intervention	Phase
Coronary Heart Disease Angina Pectoris Atherosclerosis	Drug: aspirin Drug: clopidogrel	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Aspirin Non-Responsiveness and Clopidogrel Endpoint Trial.

Resource links provided by NLM:

MedlinePlus related topics: Angina Coronary Artery Disease Heart Attack Heart Diseases

Drug Information available for: Acetylsalicylic acid Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by Ullevaal University Hospital:

Primary Outcome Measures:

Mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Myocardial infarction [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Unstable angina with ECG changes or raised levels of cardiac markers not to be classified as a myocardial infarction [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Instent restenosis and/or thrombosis detected by coronary angiography. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	1001
Study Start Date:	April 2003
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1, aspirin: Active Comparator Aspirin 160 mg	Drug: aspirin Aspirin 160 mg once daily for two years
2, clopidogrel: Active Comparator Clopidogrel 75 mg	Drug: clopidogrel clopidogrel 75 mg once daily for two years

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00222261

Locations

Norway
Ullevaal University Hospital
Oslo, Norway, 0407

Sponsors and Collaborators

Ullevaal University Hospital

The Norwegian Council for Cardiovascular Diseases.

The Scientific Board, Ullevål University Hospital.

Ada and Hagbart Waages Humanitarian and Charity Foundation

Alf and Aagot Helgesens Research Foundation.

Investigators

Principal Investigator:	Alf-Aage R. Pettersen, M.D.	Dept. of Cardiology, Ullevaal University Hospital, Oslo
Study Chair:	Harald Arnesen, M.D. Ph.D.	Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Study Director:	Ingebjorg Seljeflot, Ph.D.	Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Study Director:	Michael Abdelnoor, Ph.D.	Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Study Director:	Arne Westheim, M.D. Ph.D	Dept. of Cardiology, Ullevaal University Hospital, Oslo

More Information

Publications:

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.

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.

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.

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.

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.

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.

De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregation tests? J Thromb Haemost. 2003 Sep;1(9):2048-50. No abstract available.

Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. Review. No abstract available.

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.

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.

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.

[No authors listed] 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.

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. Summary for patients in: CMAJ. 2002 Oct 29;167(9):1036.

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.

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.

Responsible Party:	Ullevaal University Hospital, Oslo, Norway ( Alf-Aage R Pettersen, MD )
Study ID Numbers:	ASCET
Study First Received:	September 13, 2005
Last Updated:	July 3, 2008
ClinicalTrials.gov Identifier:	NCT00222261 History of Changes
Health Authority:	Norway: The National Committees for Research Ethics in Norway; Norway: Norwegian Medicines Agency; Norway: The Data Inspectorate

Keywords provided by Ullevaal University Hospital:

antiplatelet therapy
aspirin non-responders
aspirin resistance

clopidogrel
coronary heart disease
stable angina pectoris

Additional relevant MeSH terms:

Atherosclerosis
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Myocardial Ischemia
Hematologic Agents
Physiological Effects of Drugs
Angina Pectoris
Fibrinolytic Agents
Pain
Arteriosclerosis
Signs and Symptoms
Fibrin Modulating Agents
Aspirin
Sensory System Agents
Therapeutic Uses

Cardiovascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Arterial Occlusive Diseases
Heart Diseases
Cyclooxygenase Inhibitors
Vascular Diseases
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Chest Pain
Coronary Disease
Analgesics, Non-Narcotic
Clopidogrel
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010