REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction

Phase 4

Completed

• Conditions: Acute Myocardial Infarction
• Interventions: Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd

• Registration Number: NCT01381185
• Lead Sponsor: University Hospital Ostrava

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.

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-06-22
• Study First Submitted QC: 2011-06-22
• Study First Posted: 2011-06-27
• Primary Completion: 2015-06
• Study Completion: 2015-07
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-26
• Last Update Posted: 2016-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ASA/CLP increase	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

Primary Outcome Measures

Name	Time	Method
Platelet inhibition level	5 days	The main outcome measure is the difference in platelet inhibition between clopidogrel 1x75mg and 2x75mg in HPR patients

Secondary Outcome Measures

Name	Time	Method
Bleeding Events	30 days	TIMI major/minor bleeding Bleeding prediction with Crusade bleeding score (calculator free accessible at http://www.crusadebleedingscore.org/index.html)
Stent thrombosis	30 days	In-stent thrombosis will be assessed in 30-days time-frame in all patients included in the trial. -- due to inadequate power of the trial IST cannot be primary outcome measure--

Trial Locations

Locations (2)

University Hospital Ostrava; 🇨🇿 Ostrava, Poruba, Czech Republic

Departement of Laboratory Medicine, Prostejov Hospital; 🇨🇿 Prostejov, Czech Republic