Erythropoietin Effect on Ischemic_ Reperfusion Injury in Coronary Artery Bypass Graft Surgery

Study Overview
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Brief Summary
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The aim of this trail is to assess the safety and therapeutic effects of single EPO intervention in different times during coronary surgery in changes of inflammatory response.

Detailed Description
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In addition to well-known effect of Erythropoietin (EPO) on erythropoiesis in hypoxic conditions, some lines of evidence suggest its protective effects against reperfusion injury in several tissues by its specific receptor. Preclinical studies have indicated a broad variety of cardioprotective actions for EPO. It improves cardiac function and exercise capacity in congestive heart failure, angiogenesis, limit myocardial inflammatory response, cardiac remodeling, infarct size and apoptosis extension induced by reperfusion injury. Activation of EPO receptor in endothelial and cardiac cells is suggested to attenuate proinflammatory cytokines production and inflammatory cells infiltration, and increasing nitric oxide production through possible mechanisms. Reperfusion injury is unavoidable event during cardiac surgery using cardiopulmonary bypass.It is associated with inflammation, cell injury and attenuate contractility property. Although it is an area of concern and many clinical studies have been designed by different interventions, it remains a major challenge. EPO intervention during heart reperfusion (surgery/ percutaneous angioplasty) as a new promise of cardioprotection strategy is the main design of several studies with conflicting results .

Official Title
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Placebo- Controlled,Randomized,Double Blind Trial of Erythropoietin Effect on Ischemic_ Reperfusion Injury in Coronary Artery Bypass Graft Surgery

Conditions
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Myocardial Ischemic Reperfusion Injury

Intervention / Treatment
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* Drug: normal saline
* Drug: erythropoietin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Revascularization requirement according to angiographic evidence Elective coronary artery bypass graft surgery First time coronary artery bypass graft surgery On-pump coronary artery bypass graft surgery Exclusion Criteria: History of myocardial infarction in the past 3 months Previous myocardial trauma or major surgery in the past 3 months Cr>2mg/dl Receiving streptokinase or previous reperfusion treatments Erythropoietin intake in the recent 6 months Known thromboembolic disorder and malignant disease Uncontrolled hypertension Polycythemia Previous valvular surgery

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: group A<br>20000 IU erythropoietin infusion during aortic cross clamp in 45-60 minutes | Drug: erythropoietin<br> <br> * Other names: epoietin alfa;|
| Active Comparator: group B<br>20000 IU erythropoietin infusion after induction of anesthesia and before undergoing cardiopulmonary bypass pump in 45-60 minutes | Drug: erythropoietin<br> <br> * Other names: epoietin alfa;|
| Placebo Comparator: control<br>50 ml normal saline infusion during aortic cross clamp in 45-60 minutes | Drug: normal saline<br> <br> * Other names: N/S;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Interleukin 6(IL6) | Serum IL6(an inflammatory marker) level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation | Change from baseline until 48 hours after surgery | 
| Change in YKL-40 | Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40 is an inflammatory marker.Serum YKL-40 level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation | Change from baseline until 48 hours after surgery | 
| Change in pro b-type natriuretic peptide(pro BNP) | Serum pro BNP level is measured before operation (base),just after operation,24 hours after operation,48 hours after operation | Change from baseline until 48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of bleeding |  | During operation until 24 hours after surgery | 
| Need to blood transfusion | Number of packed cell and fresh frozen plasma that transfused in the period of time that patient is hospitalized. | During and after operation, through study completion,an average of one week | 
| Ventilation time |  | Period of time after surgery that patient has been intubated in ICU,an average of 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery bypass, Erythropoietin, Inflammation, IL-6, Reperfusion injury, YKL- 40