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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital Ostrava
Sponsor:
Information provided by:
University Hospital Ostrava
ClinicalTrials.gov Identifier:
NCT01381185
First received: June 22, 2011
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Acute Myocardial Infarction
Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital Ostrava:

Primary Outcome Measures:
  • Platelet inhibition level [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    The main outcome measure is the difference in platelet inhibition between clopidogrel 1x75mg and 2x75mg in HPR patients


Secondary Outcome Measures:
  • Bleeding Events [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    TIMI major/minor bleeding Bleeding prediction with Crusade bleeding score (calculator free accessible at http://www.crusadebleedingscore.org/index.html)

  • Stent thrombosis [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    unplanned targed vessel revascularisation (TVR), need for coronary - aortic by-pass graft ,myocardial infarction


Estimated Enrollment: 154
Study Start Date: May 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: R-130964

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

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01381185

Contacts
Contact: Vaclav Prochazka, MD, PhD, MSc +420597372510 vaclav.prochazka@fno.cz

Locations
Czech Republic
University Hospital Ostrava Recruiting
Ostrava, Poruba, Czech Republic, 70852
Contact: Jiri Hyncica, Bc    +420739505896    jiri.hyncica@fno.cz   
Sub-Investigator: Peter Blasko, MD         
Sub-Investigator: Radovan Stancik, MD         
Sub-Investigator: David Sipula, MD         
Departement of Laboratory Medicine, Prostejov Hospital Active, not recruiting
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
  More Information

Additional Information:
Publications:
Responsible Party: Jiri Plasek, MD, University Hospital Ostrava
ClinicalTrials.gov Identifier: NCT01381185     History of Changes
Other Study ID Numbers: FNO-KVO-1, plasek680
Study First Received: June 22, 2011
Last Updated: August 7, 2014
Health Authority: Czech Republic: Ethics Committee

Keywords provided by University Hospital Ostrava:
myocardial infarction
percutaneous coronary intervention (PCI)
high platelet reactivity (HPR)

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Aspirin
Ticlopidine
Clopidogrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 16, 2014