Intracoronary Darbepoetin-alpha to Reduce The Infarct Size and Post-Infarct Remodeling

Study Overview
=================
Brief Summary
-----------------
Prospective, randomized and open label trial Hypothesis Infusion of intracoronary darbepoetin-alpha at the time of reperfusion may reduce infarct size and post-infarct pathologic left ventricular remodeling in patients with ST-segment elevation myocardial infarction. Methods Randomization into control group or treatment group Treatment group : Darbepoetin-alpha 300ug intracoronary bolus infusion via over-the-wire balloon system simultaneously with first balloon inflation and conventional treatment Control group : conventional treatment Endpoints peak CK-MB & troponin levels : baseline,6h,12hr,18hr, 24hr, 36hr and 48hr MRI at baseline : infarct size, area at risk and salvaged myocardium MRI at 4 months : prevalence of pathologic left ventricle remodeling (definition: increase of end-diastolic volume index > 20% compared to baseline) safety endpoint : cardiac death, nonfatal myocardial infarction, stent thrombosis, ischemic stroke, hospital readmission with heart failure or ischemic symptom, bleeding and urgent target lesion revascularization

Detailed Description
-----------------
[Eligibility Criteria] 1. Patients, regardless of gender, at the age from 18 to 80 years were eligible if they had within 12 hours of onset of ST-segment myocardial infarction that was decided to treat with primary percutaneous coronary intervention. [Exclusion criteria] Uncontrolled congestive heart failure (Killip classes II and III, or cardiogenic shock) History of malignancy Serious hematological disease Current infectious disease requiring antibiotic therapy Baseline creatinine level > 2.0 mg/dL or dependence on dialysis Known hypersensitivity to or contraindication for heparin, aspirin, clopidogrel, sirolimus, everolimus, contrast medium and darbepoetin-α [Primary endpoint] Myocardial infarct size, estimated by measurement of peak levels of cardiac biomarker (CK-MB and troponin-I of the patients was followed for 48 hours at every 6 hours) [Secondary end points] The infarct size, measured as the area of delayed enhancement seen with cardiac magnetic resonance (CMR) imaging on average four days after ST-segment elevation myocardial infarction (baseline) The proportion of area at risk (AAR) and salvaged myocardium, calculated by formula; [AAR - Infarct size] / AAR X 100 (%) The change of left ventricular ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) assessed by CMR between four days and four months LV remodeling index [(LVEDV at four months - baseline LVEDV) / baseline LVEDV X 100%] and the incidence of pathologic LV remodeling (LV remodeling index > 20%); [Safety endpoints] The incidence of composites of the cardiovascular endpoints (cardiac death, nonfatal myocardial infarction, stent thrombosis, ischemic stroke, hospital readmission with heart failure or ischemic symptoms, bleeding and urgent target lesion revascularization) assessed at four months.

Official Title
-----------------
The Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion: Gauging Infarct Size in Patients With Acute ST-segment Elevation Myocardial Infarction (ICEBERG).

Conditions
-----------------
Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Darbepoetin alfa
* Drug: Control Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with ST-elevation myocardial infarction (MI) within 12 hours of onset Suitable coronary anatomy for PCI Age < 80 yrs Exclusion Criteria: Uncontrolled congestive heart failure (Killip classes II and III, or cardiogenic shock) History of malignancy Serious hematological disease Current infectious disease requiring antibiotic therapy Baseline creatinine level > 2.0 mg/dL or dependence on dialysis Known hypersensitivity to or contraindication for heparin, aspirin, clopidogrel, sirolimus, everolimus, contrast medium and darbepoetin-α

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Received same volume of saline | Drug: Control Saline<br>* Same volume of saline intracoronary bolus infusion via over-the-wire balloon before the 1st ballooning and conventional treatment<br>* Other names: 0.9% normal saline;|
| Active Comparator: Darbepoetin group<br>Darbepoetin alfa 300ug intracoronary bolus infusion via over-the-wire balloon before the 1st ballooning & conventional treatment | Drug: Darbepoetin alfa<br>* Darbepoetin alfa 300ug intracoronary bolus infusion via over-the-wire balloon before the 1st ballooning and conventional treatment<br>* Other names: Nesp PFS Prefilled Syringe (Jeilkirin Pharm. Korea);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak CK-MB/ Troponin-I levels |  | baseline, 6, 12,18,24,36,48hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct size, area at risk and proportion of salvaged myocardium | Assessed by cardiac MRI | Participants will be followed for the duration of hospital stay, an expected average of 4 days | 
| Pathologic left ventricle remodeling assessed by cardiac MRI | Definition : Increase of end-diastolic volume of left ventricle >20% | 4 months | 
| Change of left ventricular ejection fraction, LV end-diastolic volume , and LV end-systolic volume assessed by cardiac MRI |  | Between four days and 4 months | 
| Composites of cardiovascular endpoints | ccardiac death, nonfatal myocardial infarction, stent thrombosis, ischemic stroke, hospital readmission with heart failure or ischemic symptoms, bleeding and target lesion revascularization | 4 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Myocardial infarction, Erythropoietin, Myocardial reperfusion injury