Clinical trial NCT01863134: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non ST Elevation Myocardial Infarction
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
First posted: 2013-05-27
Enrollment: 140
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility 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

Primary outcomes:
measure: Major Adverse Cardiac and Cerebrovascular Events (MACCE)
timeFrame: Up to 12 month
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Katowice
country: Poland
facility: First Department of Cardiac Surgery, Medical University of Silesia
state: Slaskie
city: Katowice
country: Poland
facility: Center for Cardiovascular Research and Development, American Heart of Poland
city: Katowice
country: Poland
facility: Department of Internal Medicine and Clinical Pharmacology
city: Katowice
country: Poland
facility: First Department of Cardiology, Medical University of Silesia
city: Krakow
country: Poland
facility: Division of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College
Study officials:
affiliation: Medical University of Silesia
name: Miroslaw Wilczynski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: