Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.

NCT ID: NCT00222261

Last Updated: 2011-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1001 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-04-30

Study Completion Date

2010-07-31

Brief Summary

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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

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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.

Conditions

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Coronary Heart Disease Angina Pectoris Atherosclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1, aspirin

Aspirin 160 mg

Group Type ACTIVE_COMPARATOR

aspirin

Intervention Type DRUG

Aspirin 160 mg once daily for two years

2, clopidogrel

Clopidogrel 75 mg

Group Type ACTIVE_COMPARATOR

clopidogrel

Intervention Type DRUG

clopidogrel 75 mg once daily for two years

Interventions

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aspirin

Aspirin 160 mg once daily for two years

Intervention Type DRUG

clopidogrel

clopidogrel 75 mg once daily for two years

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Norwegian Council for Cardiovascular Diseases.

UNKNOWN

Sponsor Role collaborator

Ada and Hagbart Waages Humanitarian and Charity Foundation

OTHER

Sponsor Role collaborator

Alf and Aagot Helgesens Research Foundation.

UNKNOWN

Sponsor Role collaborator

Ullevaal University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ullevaal University Hospital, Oslo, Norway

Principal Investigators

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Alf-Aage R. Pettersen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Dept. of Cardiology, Ullevaal University Hospital, Oslo

Harald Arnesen, M.D. Ph.D.

Role: STUDY_CHAIR

Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo

Ingebjorg Seljeflot, Ph.D.

Role: STUDY_DIRECTOR

Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo

Michael Abdelnoor, Ph.D.

Role: STUDY_DIRECTOR

Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo

Arne Westheim, M.D. Ph.D

Role: STUDY_DIRECTOR

Dept. of Cardiology, Ullevaal University Hospital, Oslo

Locations

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Ullevaal University Hospital

Oslo, , Norway

Site Status

Countries

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Norway

References

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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. doi: 10.1136/bmj.324.7329.71.

Reference Type BACKGROUND
PMID: 11786451 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7889440 (View on PubMed)

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. doi: 10.1016/0049-3848(91)90085-b.

Reference Type BACKGROUND
PMID: 1780803 (View on PubMed)

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. doi: 10.1016/s0002-9149(01)01631-9.

Reference Type BACKGROUND
PMID: 11472699 (View on PubMed)

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. doi: 10.1161/01.str.25.12.2331.

Reference Type BACKGROUND
PMID: 7974569 (View on PubMed)

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. doi: 10.1080/14017439850140021.

Reference Type BACKGROUND
PMID: 9802142 (View on PubMed)

De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregation tests? J Thromb Haemost. 2003 Sep;1(9):2048-50. doi: 10.1046/j.1538-7836.2003.00354.x. No abstract available.

Reference Type BACKGROUND
PMID: 12941050 (View on PubMed)

Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. doi: 10.1046/j.1538-7836.2003.00284.x. No abstract available.

Reference Type BACKGROUND
PMID: 12911581 (View on PubMed)

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. doi: 10.1016/0049-3848(93)90164-j.

Reference Type BACKGROUND
PMID: 8236166 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11109035 (View on PubMed)

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. doi: 10.1016/s0735-1097(02)03014-0.

Reference Type BACKGROUND
PMID: 12651041 (View on PubMed)

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. doi: 10.1016/s0140-6736(96)09457-3.

Reference Type BACKGROUND
PMID: 8918275 (View on PubMed)

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. doi: 10.1056/NEJMoa020496.

Reference Type BACKGROUND
PMID: 12324552 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12586130 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15804802 (View on PubMed)

Opstad TB, Nordeng J, Pettersen AR, Akra S, Bratseth V, Zaidi H, Helseth R, Solheim S, Seljeflot I. The NLRP3 Genetic Variant (rs10754555) Reduces the Risk of Adverse Outcome in Middle-Aged Patients with Chronic Coronary Syndrome. J Immunol Res. 2022 Dec 20;2022:2366695. doi: 10.1155/2022/2366695. eCollection 2022.

Reference Type DERIVED
PMID: 36582742 (View on PubMed)

Warlo EMK, Bratseth V, Pettersen AR, Holme PA, Arnesen H, Seljeflot I, Opstad TB. Genetic Variation in ADAMTS13 is Related to VWF Levels, Atrial Fibrillation and Cerebral Ischemic Events. Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221141893. doi: 10.1177/10760296221141893.

Reference Type DERIVED
PMID: 36474435 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29200971 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23130135 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22883224 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22141572 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21426546 (View on PubMed)

Other Identifiers

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ASCET

Identifier Type: -

Identifier Source: org_study_id

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