Clinical Effects of Eptifibatide Administration in High Risk Patients Presenting With Non-ST Segment Elevation Acute Coronary Syndrome (NSTE-ACS) Requiring Urgent Coronary Artery Bypass Graft Surgery in Short- and Long-Term Follow-up
Information source: Medical University of Silesia
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Non ST Elevation Myocardial Infarction
Intervention: Eptifibatide (Drug); Placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Medical University of Silesia Official(s) and/or principal investigator(s): Miroslaw Wilczynski, MD, PhD, Principal Investigator, Affiliation: Medical University of Silesia
Summary
1. INTRODUCTION
Through last couple of years the number of patients treated for acute coronary event
without persistent ST segment elevation in ECG has been growing.
This is probably an effect of improving diagnostics of myocardial infraction without
persistent ST segment elevation in ECG, due to routine Troponin serum level evaluation
and better primary prevention.
This fact makes the search for the optimal treatment for patients with acute coronary
event without persistent ST segment elevation in ECG, including both patients intended
for pharmacological and invasive treatment percutaneous coronary intervention (PCI) or
coronary artery byppass grafting (CABG).
Patients undergoing invasive treatment for acute coronary event, have higher risk rate,
than those with stabile angina pectoris.
The authors of this study want to evaluate, whether the proportional use of platelet
GP IIb/IIIa receptor antagonist - eptifibatide in patients undergoing CABG results in
improvement of short-, and long time results in those patients.
Eptifibatide ( Integrilin) a cyclic heptapeptide antagonist of the GP IIb/IIIa integrin
receptor, is an intravenous antagonist with rapid onset and short half-life.
2. STUDY RATIONALE
The notion acute coronary syndrome (ACS) includes several clinical situations, such a
unstable coronary artery disease, non-Q wave myocardial infarction and Q wave myocardial
infarction.
On the basis of 12-lead ECG, patients with acute coronary syndrome (ACS) can be divided into
two groups: with and without ST segment elevation.
Another stratification factor in patients with ACS, especially these without ST elevation is
evaluation of biochemical markers of myocardial necrosis, such as Troponins (TnI, TnT) and
creatinine kinase isoenzymes (CK-MB). Serum concentrations of these markers allow to
distinguish myocardial infarction (elevation of markers' concentration) from unstable
coronary artery disease.
All ACS have common etiopathogenesis which is plaque rupture, thrombus formation in the
lumen of coronary artery.
Platelets are the key factor in this process. Platelets by means of their collagen and von
Willebrand factor glycoprotein receptors bind to damaged artery wall. Simultaneously many
factors cause platelet activation, which leads to changes in their shape, release of
intraplatelet components and activation of fibrinogen-binding glycoprotein receptors
IIb/IIIa (GP IIb/IIIa). Activated form of GP IIb/IIIa binds to GP IIb/IIIa of another
platelet by means of fibrinogen molecule. Fibrinogen molecules form stable bridges between
platelets. This process is referred to as aggregation, and leads to clot formation, which is
further stabilized by fibrine fibres.
In this way the intravascular thrombus is formed, which after totally occluding the arterial
lumen causes acute ischemia of the relevant region of myocardium and subsequently its
infarction.
The key role of GP IIa/IIIb in the process of platelet clot formation has important
therapeutic consequences. By now several specific (direct) and non-specific (indirect)
antagonists of GP IIb/IIIa have been developed.
There are indirect antagonists as acetylsalicylic acid, ticlopidine and clopidogrel and
direct antagonists as abciximab, tirofiban and eptifibatide Additionally also anticoagulants
(heparin, LMWH - low molecular weight heparin) have antiplatelet properties by inhibiting
thrombin production.
Clinical studies performed all over the world have proven the efficacy and safety of three
agents from the GP Iia/IIIb group: abciximab, tirofiban and eptifibatide.
In several big clinical studies (EPIC, EPILOG, EPISTENT, ESPRIT, CAPTURE, PURSUIT,
PRISM-PLUS, TACTICS-TIMI 18) the high efficacy of these drugs was showed in patients with
ACS without ST segment elevation undergoing mainly percutaneous transluminal coronary
angiography (PTCA) and stenting. The use of GP IIa/IIIb antagonists in this group of
patients significantly reduces the death and myocardial infarction (MI) rate during early as
well as late follow-up period. Moreover, last observations indicate, that the biggest
benefit from such therapeutic strategy is observed in high risk patients; those with
diabetes, high troponin levels and ECG changes.
During last years, there is an increase in frequency of ACS without ST segment elevation.
This is probably due to improved diagnostics of MI without ST elevation basing on routine
troponin evaluation, but also thanks to better primary prevention.
Therefore determining an optimal therapeutic strategy for patients with ACS without ST
segment elevation remains a crucial issue.
It concerns patients qualified to medical treatment as well as those qualified to invasive
procedures (PTCA or CABG).
Clinical Details
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment
Primary outcome: Major Adverse Cardiac and Cerebrovascular Events (MACCE)
Eligibility
Minimum age: 21 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Subjects must have a typical anginal pain lasting at least 20 min., but no longer
than 24h.
- ECG confirming ischaemia
- ST segment depression >= 1,0 mm in at least 2 leads, or,
- negative T waves >= 2,0 mm in at least 2 leads.
- Positive troponin I (TnI).
- Subjects must demonstrate their willingness to participate in the study and comply
with its procedures by signing a written informed consent and/or parent or legal
guardian must have signed a written informed consent.
- Subjects must be ≥ 21 year of age, of either sex and any race.
- Women of childbearing potential (includes women who are less than 1 year
postmenopausal and women who become sexually active) must be using an acceptable
method of birth control (e. g., hormonal contraceptive, medically prescribed IUD -
intrauterine device, condom in combination with spermicide) or be surgically
sterilized (e. g., hysterectomy or tubal ligation).
- Subjects must be free of any clinically significant disease that would interfere with
study evaluations (see exclusion criteria).
- Subjects must understand and be able to adhere to the dosing and visit schedules, and
agree to record concomitant medications and adverse events.
Exclusion Criteria:
- Women who are pregnant or nursing.
- Subjects who have not observed the designated washout periods for any of the
prohibited medications.
- Subjects who have used any investigational product within 30 days prior to
enrollment.
- Subjects who have the following clinical conditions are excluded:
Patients with:
- Angina lasting longer than 24h.
- ST segment elevation - Pardy wave
- age over 75 years
- history of revascularization procedure during last 6 months (PTCA, CABG)
- chronic heart failure (NYHA III or IV) during pre-hospitalization period
- history of bleeding from gastrointestinal tract or genitourinary system during last
30 days
- history of intracranial lesions or stroke
- history of major surgery or trauma during last 6 weeks
- history of hemorrhagic diathesis
- thrombocytopenia < 100 000/mm3
- anticoagulant therapy with INR>2,0
- significant hepatic failure
- significant renal failure with serum creatinine>2,0 mg%
- elevated blood pressure: SBP>200mmHg and/or DBP>110mmHg despite the antihypertensive
treatment
- allergy to drugs or any therapeutic agent
Locations and Contacts
Center for Cardiovascular Research and Development, American Heart of Poland, Katowice, Poland
Department of Internal Medicine and Clinical Pharmacology, Katowice, Poland
First Department of Cardiology, Medical University of Silesia, Katowice, Poland
Division of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College, Krakow, Poland
Albert Einstein College of Medicine, New York, New York, United States
First Department of Cardiac Surgery, Medical University of Silesia, Katowice, Slaskie 40-635, Poland
Additional Information
Starting date: January 2005
Last updated: August 19, 2013
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