Erythropoietin and Pediatric Cardiac Surgery (EPO)

Lack of bloodflow to the heart and brain when the heart is stopped during heart surgery can cause damage to those organs. We hypothesize that a single dose of erythropoietin prior to the heart bypass portion of surgery may protect the infant human heart and brain from injury.

This randomized clinical trial will involve 120 children, age 6 weeks to 18 years, requiring heart bypass surgery for congenital heart defects.

Study Overview

• Status: Terminated
• Conditions: Congenital Heart Defect
• Intervention / Treatment: Drug: acyanotic placebo; Drug: acyanotic erythropoietin

Detailed Description

Lack of bloodflow to the heart and brain when the heart is stopped during heart surgery can cause damage to those organs. A medicine already used in humans, erythropoietin, may protect the heart and brain of children born with heart defects during their surgical repair. In a rabbit model, erythropoietin did protect the hearts. We hypothesize that a single dose of erythropoietin prior to the heart bypass portion of surgery may protect the infant human heart and brain from injury.

For this randomized control trial, 120 children, age 6 weeks to 18 years, requiring heart bypass surgery for congenital heart defects, will be divided into four groups. Two groups will be children whose usual blood oxygen level is low because of their heart defect; the other two will be children with normal blood oxygen levels. Each child will be randomized to receive either erythropoietin or placebo 15 minutes prior to stopping the heart during their surgery.

Erythropoietin's protective function will be measured after surgery by: (1) amount of medication required to support heart function, (2) how well the heart pumps blood as seen by echocardiogram, (3) levels of chemicals produced by the body when heart or brain tissue injury occurs, (4) urine output and oxygen levels (5) time on ventilator support (6) ICU stay and (7) hospital stay. Heart tissue will be collected during surgery to determine how erythropoietin protects heart cells.

Statistical tests including ANOVA will test for similarities and differences among the groups on the measures of protection from injury.

Note - the study design was edited after the FDA released a warning about the use of erythropoietin. Only acyanotic patients were recruited therefore only 2 study groups are included.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 6 weeks to 18 years
• Requiring open heart surgery for congenital heart defect -Parents able to speak English and document informed consent -

Exclusion Criteria:

• Received erythropoietin within past 30 days
• Previous adverse reaction to erythropoietin or to albumin
• History of neurological disorder -Laboratory evidence of kidney or liver dysfunction -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 3; acyanotic placebo	Drug: acyanotic placebo; Single dose IV push
Experimental: 4; acyanotic erythropoietin	Drug: acyanotic erythropoietin; Single dose IV push

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Markers of Heart Damage	Troponin I levels (ng/ml) measured at 4 time points	4 postoperative time points up to 48 hours
Biochemical Markers of Neuron Damage		4 postoperative time points
Echocardiographic Assessment of Heart Function		24 hours postop

Secondary Outcome Measures

Outcome Measure	Time Frame
Inotropic Support	24 and 48 hours post operative
Length of Hospitalization	At hospital discharge, up to 30 days

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Collaborators: National Center for Research Resources (NCRR); Children's Hospital and Health System Foundation, Wisconsin
• Investigators: Principal Investigator: John Baker, PhD, Medical College of Wisconsin; Principal Investigator: Steve Zangwill, MD, Children's Hospital and Health System Foundation, Wisconsin

Publications and helpful links

General Publications

• Shi Y, Rafiee P, Su J, Pritchard KA Jr, Tweddell JS, Baker JE. Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol. 2004 May;99(3):173-82. doi: 10.1007/s00395-004-0455-x. Epub 2004 Jan 29. Erratum In: Basic Res Cardiol. 2004 May;99(3):239.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: March 22, 2007
• First Submitted That Met QC Criteria: March 22, 2007
• First Posted (Estimate): March 23, 2007

Study Record Updates

• Last Update Posted (Actual): November 8, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Erythropoietin; Congenital heart surgery
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Hematinics; Epoetin Alfa
• Other Study ID Numbers: CHW 04/161