REACT-MI: REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction

Sponsor

University Hospital Ostrava (Other)

Overall Status

Completed

CT.gov ID

NCT01381185

Collaborator

(none)

154

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarction	Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd	Phase 4

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 - CYP2C192 and CYP2C93 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 Design

Study Type:

Interventional

Actual Enrollment :

154 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

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 Start Date :

May 1, 2011

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard therapy standard dose of 100mg aspirin qd and 1x75mg Clopidogrel will be given
Active Comparator: ASA/CLP increase According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd	Drug: 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) Other Names: R-130964

Arm

Intervention/Treatment

No Intervention: Standard therapy

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

Active Comparator: ASA/CLP increase

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

Drug: 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)

Other Names:

R-130964

Outcome Measures

Primary Outcome Measures

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

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--

Other Outcome Measures

Ischaemic events (not IST) [30 days]
unplanned targed vessel revascularisation (TVR), need for coronary - aortic by-pass graft ,myocardial infarction

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Ostrava	Ostrava	Poruba	Czech Republic	70852
2	Departement of Laboratory Medicine, Prostejov Hospital	Prostejov		Czech Republic	79604

Sponsors and Collaborators

University Hospital Ostrava

Investigators

Principal Investigator: Jiri Plasek, MD, PhD, Department of Cardiology, University Hospital Ostrava
Study Chair: Miroslav Homza, MD, Department of Cardiology, University Hospital Ostrava
Study Chair: Jaromir Gumulec, MD, Institute of clinical Hematology, University Hospital Ostrava