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
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|ClinicalTrials.gov Identifier: NCT01863134|
Recruitment Status : Completed
First Posted : May 27, 2013
Results First Posted : October 31, 2013
Last Update Posted : October 31, 2013
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.
- 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).
|Condition or disease||Intervention/treatment||Phase|
|Non ST Elevation Myocardial Infarction||Drug: Eptifibatide Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|Study Start Date :||January 2005|
|Actual Primary Completion Date :||December 2010|
|Actual Study Completion Date :||December 2010|
Patients were given a bolus of eptifibatide (Integrillin; 180µg/kg of body weight) and an intravenous infusion of 2 µg/kg/min followed by acetylsalicylic acid (150mg orally daily until the day of the procedure) and enoxaparin (1mg/kg subcutaneous - with the last dose 12 hours before surgery).
Other Name: In the active treatment arm patients were additionally treated with eptifibatide (Integrillin; 180µg/kg of body weight) at an infusion rate 2 µg/kg/min
Placebo Comparator: Placebo
Patients were given placebo infusion (0,9% Natrium Chloride) and an intravenous infusion of 2 µg/kg/min followed by acetylsalicylic acid (150mg orally daily until the day of the procedure) and enoxaparin (1mg/kg subcutaneous - with the last dose 12 hours before surgery).
- Major Adverse Cardiac and Cerebrovascular Events (MACCE) [ Time Frame: Up to 12 month ]MACCE was defined as combined death, nonfatal myocardial infarction, cerebrovascular event (stroke) and the need for re-hospitalization due to recurrent ischemia up to 12 months follow-up
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01863134
|United States, New York|
|Albert Einstein College of Medicine|
|New York, New York, United States|
|First Department of Cardiac Surgery, Medical University of Silesia|
|Katowice, Slaskie, Poland, 40-635|
|Center for Cardiovascular Research and Development, American Heart of Poland|
|Department of Internal Medicine and Clinical Pharmacology|
|First Department of Cardiology, Medical University of Silesia|
|Division of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College|
|Principal Investigator:||Miroslaw Wilczynski, MD, PhD||Medical University of Silesia|