Clinical trial NCT00222261: Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
Official title: Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Heart Disease
Angina Pectoris
Atherosclerosis
Keywords: antiplatelet therapy
aspirin non-responders
aspirin resistance
clopidogrel
coronary heart disease
stable angina pectoris
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: The Norwegian Council for Cardiovascular Diseases.
name: Ada and Hagbart Waages Humanitarian and Charity Foundation
name: Alf and Aagot Helgesens Research Foundation.
First posted: 2005-09-22
Enrollment: 1001
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Mortality
timeFrame: 2 years
measure: Myocardial infarction
timeFrame: 2 years
measure: Unstable angina with ECG changes or raised levels of cardiac markers not to be classified as a myocardial infarction
timeFrame: 2 years
Secondary outcomes:
measure: Instent restenosis and/or thrombosis detected by coronary angiography.
timeFrame: 2 years
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Ullevaal University Hospital
Study officials:
affiliation: Dept. of Cardiology, Ullevaal University Hospital, Oslo
name: Alf-Aage R. Pettersen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
name: Harald Arnesen, M.D. Ph.D.
role: STUDY_CHAIR
affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
name: Ingebjorg Seljeflot, Ph.D.
role: STUDY_DIRECTOR
affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
name: Michael Abdelnoor, Ph.D.
role: STUDY_DIRECTOR
affiliation: Dept. of Cardiology, Ullevaal University Hospital, Oslo
name: Arne Westheim, M.D. Ph.D
role: STUDY_DIRECTOR
References:
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citation: 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. doi: 10.1016/s0049-3848(02)00405-x.
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. doi: 10.1080/14017430410024324.
citation: Warlo EMK, Pettersen AR, Arnesen H, Seljeflot I. vWF/ADAMTS13 is associated with on-aspirin residual platelet reactivity and clinical outcome in patients with stable coronary artery disease. Thromb J. 2017 Nov 22;15:28. doi: 10.1186/s12959-017-0151-3. eCollection 2017.
citation: Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H. High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial). J Am Heart Assoc. 2012 Jun;1(3):e000703. doi: 10.1161/JAHA.112.000703. Epub 2012 Jun 22.
citation: Bratseth V, Pettersen AA, Opstad TB, Arnesen H, Seljeflot I. Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment. Thromb J. 2012 Aug 10;10(1):12. doi: 10.1186/1477-9560-10-12.
citation: Opstad TB, Pettersen AA, Arnesen H, Seljeflot I. Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an observational study. Cardiovasc Diabetol. 2011 Dec 5;10:110. doi: 10.1186/1475-2840-10-110.
citation: Pettersen AA, Arnesen H, Opstad TB, Seljeflot I. The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel. Thromb J. 2011 Mar 22;9:4. doi: 10.1186/1477-9560-9-4.