REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction

NCT ID: NCT01381185

Last Updated: 2016-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-07-31

Brief Summary

The purpose of this study is to compare 3 point-of-care methods for monitoring antiplatelet therapy to golden standard (Light transmittance aggregometry-LTA) in high risk population of acute myocardial infarction patients. If two methods (PFA-100, VerifyNOW,Multiplate or LTA) will indicate insufficient antiplatelet blockade/high residual reactivity for aspirin, clopidogrel or both, the dose of aspirin will be increased to 200mg qd and the dose of clopidogrel will be increased to 2x75mg qd.In addition genotyping of CYP2C19 (6 alleles) will be performed.

Detailed Description

Dual antiplatelet therapy is the cornerstone of treatment of coronary heart disease after coronary stent implantation. The interindividual response to this therapy is not uniform, however. There are subgroups of patients, where no anticipated antiplatelet effect to either aspirin, clopidogrel or both is reached. The term of aspirin/clopidogrel resistance has been introduced few years ago, most recently it was substituted by more suitable term - high on-treatment residual platelet reactivity (HPR). Although there are many assays to monitor antiplatelet therapy, uncertainty still remains about the correlation of HPR with ischemic vascular events (in-stent thrombosis, myocardial infarction, etc.). Thus platelet aggregation testing is considered to be the most promising method to indicate inappropriate/low response to aspirin/clopidogrel, however the best suited method is not established yet. Up-to date light transmittance aggregometry is widely accepted as golden standard, nonetheless labour intensive and difficult to standardize. On the other hand many point-of-care aggregation testing methods like PFA-100, VerifyNOW, Multiplate etc. have been introduced, their role in clinical practice is uncertain, however. The biggest challenge of today is to determine platelet function assay, which could reliably indicate future ischemic vascular events;moreover it could be potentially used to tailor antiplatelet therapy and precede these events. It was demonstrated, that gene polymorphism - CYP2C19*2 and CYP2C9*3 loss of function is conjugated with an increased occurrence of stent thrombosis. Within the project we also plan to examine 4 alleles which have not been examined in detail before.

Conditions

Acute Myocardial Infarction

Keywords

myocardial infarction; percutaneous coronary intervention (PCI); high platelet reactivity (HPR)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Standard therapy

standard dose of 100mg aspirin qd and 1x75mg Clopidogrel will be given

Group Type: NO_INTERVENTION

No interventions assigned to this group

ASA/CLP increase

According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd

Group Type: ACTIVE_COMPARATOR

Aspirin 200mg qd, Clopidogrel 2x75mg qd

Intervention Type: DRUG

According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd. This treatment will be given for 30 days from index event (myocardial infarction)

Interventions

Aspirin 200mg qd, Clopidogrel 2x75mg qd

According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd. This treatment will be given for 30 days from index event (myocardial infarction)

Intervention Type: DRUG

Other Intervention Names

R-130964

Eligibility Criteria

Inclusion Criteria

• acute myocardial infarction (verified by troponin I elevation and ST-segment deviation ≥0.1mV in ≥2 contiguous ECG leads persisting for at least 20 minutes and angiographical proof of coronary stenosis )
• preceding antiplatelet medication with aspirin100mg qd/5 and more days before PCI
• pre-treatment with 600mg Clopidogrel loading dose
• preferably patients with drug eluting stent implantation
• signed informed consent

Exclusion Criteria

• stable/unstable angina pectoris
• active malignancy
• contraindication to antiplatelet therapy
• increased risk of bleeding (trauma, surgery or non-ischemic stroke in last month)
• effective anticoagulation therapy:LMWH, Pradaxa, Xarelto, Warfarin
• known thrombophile disorder
• SIRS
• renal insufficiency (eGFR under 15ml/min)
• severe anemia (<80 g/l)
• polyglobulia (>160 g/l)
• pregnancy
• Hematocrit <0.25 > 0.55

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Ostrava

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jiri Plasek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, University Hospital Ostrava

Miroslav Homza, MD

Role: STUDY_CHAIR

Department of Cardiology, University Hospital Ostrava

Jaromir Gumulec, MD

Role: STUDY_CHAIR

Institute of clinical Hematology, University Hospital Ostrava

Locations

University Hospital Ostrava

Ostrava, Poruba, Czechia

Departement of Laboratory Medicine, Prostejov Hospital

Prostějov, , Czechia

Countries

Czechia

References

Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation. 2009 Jan 20;119(2):237-42. doi: 10.1161/CIRCULATIONAHA.108.812636. Epub 2008 Dec 31.

Reference Type: BACKGROUND

PMID: 19118249 (View on PubMed)

Cuisset T, Cayla G, Frere C, Quilici J, Poyet R, Gaborit B, Bali L, Morange PE, Alessi MC, Bonnet JL. Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment? EuroIntervention. 2009 Aug;5(3):325-9. doi: 10.4244/51.

Reference Type: BACKGROUND

PMID: 19736156 (View on PubMed)

Sibbing D, Byrne RA, Bernlochner I, Kastrati A. High platelet reactivity and clinical outcome - fact and fiction. Thromb Haemost. 2011 Aug;106(2):191-202. doi: 10.1160/TH11-01-0040. Epub 2011 Apr 20.

Reference Type: BACKGROUND

PMID: 21505714 (View on PubMed)

Related Links

http://www.fno.cz

Site info

Other Identifiers

plasek680

Identifier Type: OTHER

Identifier Source: secondary_id

FNO-KVO-1

Identifier Type: -

Identifier Source: org_study_id