Clinical trial NCT01381185: REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction
Official title: Phase IV Study of Aspirin and Clopidogrel Therapy Tailored by Functional Thrombocyte Examination (PFA-100, LTA and VerifyNOW) in Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Keywords: myocardial infarction
percutaneous coronary intervention (PCI)
high platelet reactivity (HPR)
Lead sponsor: University Hospital Ostrava
Sponsor class: OTHER
First posted: 2011-06-27
Enrollment: 154
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Platelet inhibition level
timeFrame: 5 days
Secondary outcomes:
measure: Bleeding Events
timeFrame: 30 days
measure: Stent thrombosis
timeFrame: 30 days
Other outcomes:
measure: Ischaemic events (not IST)
timeFrame: 30 days
Locations:
city: Ostrava
country: Czech Republic
facility: University Hospital Ostrava
state: Poruba
city: Prostejov
country: Czech Republic
facility: Departement of Laboratory Medicine, Prostejov Hospital
Study officials:
affiliation: Department of Cardiology, University Hospital Ostrava
name: Jiri Plasek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology, University Hospital Ostrava
name: Miroslav Homza, MD
role: STUDY_CHAIR
affiliation: Institute of clinical Hematology, University Hospital Ostrava
name: Jaromir Gumulec, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.