Study of the Use of a Single Dose of Erythropoietin to Treat Acute Myocardial Ischemia

Summary

This is a phase 2 study that evaluates the effect of intravenous administration of a bolus EPO on the activation of EPOR-signal transduction cascades and myocardial apoptosis during cardiopulmonary bypass surgery. Human atrial and ventricular tissue will be collected during CABG surgery for 3-vessel disease for the assay of EPOR signaling and apoptosis. Two atrial specimens will be collected before and at the end of cardiopulmonary bypass (CPB). Concomitantly, two transmural ventricular biopsies will be obtained, at the start and at the end of CPB. Immediately after obtaining the first atrial biopsy, one bolus of EPO will be administered intravenously. The atrial tissue will be split and appropriate sections will be frozen for determination of baseline expression or activity of a number of molecules including Erk1/2, STAT5, Akt and caspase-3 or embedded in paraffin for immunohistochemistry. Ventricular tissue will only be processed for immunohistochemistry. Additionally, plasma will be collected before the procedure and for up to 30 days post-procedure to examine release of markers of both myocardial ischemia and stress (CK-MB, Troponin T and NT-proBNP) and renal dysfunction (cystatin C, creatinine for eGFR). Before initializing the randomised study, a pilot study will be performed with 5 subjects that will not be treated to evaluate the feasibility of myocardial sample collection. Initiation of the randomised study will only commence if baseline activity of EPOR-STC can be determined in the atrial tissue and caspase-3 positive cells can be identified in the second ventricular biopsy.

Conditions

• CABG
• Coronary Artery Disease

Interventions

DRUG

Epoetin alpha

A single dose of epoetin alpha during CABG for three vessel disease, 60.000 IU intravenously.

DRUG

NaCl 0.9%

A single dose of NaCl 0.9% during CABG for three vessel disease, 1 ml intravenously.

Sponsors & Collaborators

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• W. H. van Gilst, Prof, dr · University Medical Center Groningen, Dept. of Exprimental Cardiology

• W. T. Ruifrok, MD · University Medical Center Groningen, Dept. of Experimental Cardiology

• B. D. Westenbrink, MD · University Medical Center Groningen, Dept. of Experimental Cardiology

• A. H. Epema, dr, MD · University Medical Center Groningen, Dept. of Anaesthesiology

• H. E. Mungroop, dr, MD · University Medical Center Groningen, Dept. of Anaesthesiology

• P. W. Boonstra, Prof, dr, MD · University Medical Center Groningen, Dept. of Cardiothoracic Surgery

• R. A. de Boer, dr, MD · University Medical Center Groningen, Dept of Cardiology

• D. J. van Veldhuisen, Prof, dr, MD · University Medical Center Groningen, Dept. of Cardiology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2011-01-31

Completion

2011-04-30

Countries

• Netherlands

Study Locations