Erythropoetin Neuroprotection for Neonatal Cardiac Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Dana Foundation
Texas Children's Hospital
Information provided by (Responsible Party):
Dean Andropoulos, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00513240
First received: August 7, 2007
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

Brain problems occur in neonatal open heart surgery with a frequency of 20-70%, seen on neurological examination, brain imaging such as magnetic resonance imaging (MRI), or long term development problems such as learning disorders and hyperactivity syndromes. This study aims to determine if erythropoetin, a natural hormone made in the body, protects the brain from damage when given in high doses before and during neonatal open heart surgery. We will use brain MRI, brain wave tests (EEG), neurological examination, and long term developmental outcome testing to see if erythropoetin is better than salt water injection (placebo) in protecting the brain.


Condition Intervention Phase
Congenital Heart Disease
Hypoplastic Left Heart Syndrome
Transposition of the Great Arteries
Aortic Arch Hypoplasia or Interruption
Drug: Erythropoetin
Drug: Normal saline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Erythropoetin Neuroprotection for Neonatal Cardiac Surgery

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • MRI Severity of Injury Score [ Time Frame: 7 days postoperatively. ] [ Designated as safety issue: Yes ]
    MRI severity of injury score change from preoperative brain MRI to 7 day postoperative MRI(decrease by 25%). Scoring of infarction, hemorrhage, white matter injury, cerebral venous sinus thrombosis, or increased lactate on MR spectroscopy.

  • Scores on Bayley Scales of Infant Development III at Age 1 Years. [ Time Frame: 1 year postoperatively ] [ Designated as safety issue: No ]
    3 domains of the Bayley Scales of Infant Development III: Cognitive, Language and Motor Minimum score = 45, maximum score = 155; Population mean = 100, SD = 15; Higher scores are indicative of better outcomes Language scores are reflective of receptive communication and expressive communication subscales. Motor scores are reflective of fine motor and gross motor subscales.


Secondary Outcome Measures:
  • EEG Seizure Burden in the First 72 Postoperative Hours. (Total Minutes of EEG Seizures). [ Time Frame: 72 hours postoperatively. ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of High Dose Erythropoetin: 7 Erythropoetin Levels in First 24 Hours After First Dose. [ Time Frame: 24 hours after first EPO dose. ] [ Designated as safety issue: Yes ]

Enrollment: 62
Study Start Date: September 2006
Estimated Study Completion Date: September 2016
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPO group
Patients randomized to receive the 3 doses of erythropoetin.
Drug: Erythropoetin
Erythropoetin 500 units/kg IV x 3 : dose 1. 12-72 hours preoperatively, dose 2. Postoperative day #1, 48 hours after separating from cardiopulmonary bypass, and dose 3. postoperative day #3, 48 hours after dose #2
Other Names:
  • Procrit
  • Epoetin alpha
Placebo Comparator: Control group.
Patients randomized to receive 3 doses of normal saline control.
Drug: Normal saline

Normal saline placebo in 3 doses:dose 1. 12-72 hours preoperatively, dose 2. Postoperative day #1, 48 hours after separating from cardiopulmonary bypass, and dose 3. postoperative day #3, 48 hours after dose #2.

.

Other Name: Saline placebo

Detailed Description:

Hypothesis: Erythropoetin (EPO) will protect the neonatal brain in the perioperative period for congenital heart surgery.

Using a prospective, randomized, placebo-controlled, double-blinded design, the specific aims of this study are:

  1. To determine the effect of perioperative EPO on short and long term neurological outcomes in neonates undergoing cardiac surgery with an optimized cardiopulmonary bypass strategy.
  2. To determine EPO tolerability and safety with short term administration.
  3. To determine EPO pharmacokinetics in this population.
  4. To determine the relationship of neurological monitoring, specifically NIRS, to neurological outcomes with an optimized cardiopulmonary bypass technique in neonates that avoids deep hypothermic circulatory arrest, and to determine if EPO affects this relationship.

Protocol: Neonates undergoing arterial switch, Norwood, or aortic arch advancement/other complete 2 ventricle repair, >35 weeks gestation and ≥2.0 kg are eligible.

Preop day 1:NIRS for 12-24 hours, neuro exam, and Study drug dose #1: EPO 500 units/kg or saline placebo 12-72 hours before surgery. EPO Pharmacokinetic data for 25-50 consenting patients.

Day of surgery: Brain MRI immediately preop. Anesthesia/CPB per our standard practice (fentanyl 100-200 mcg/kg, midazolam, isoflurane, epsilon-aminocaproic acid, 75 mg/kg IV load to patient and CPB prime, and 75 mg/kg/hr infusion in OR) with ACP guided by TCD, pH stat, hct 30-35, avoid DHCA.

POD #1: Study drug dose #2: EPO 500 units/kg or saline placebo 24 hours after dose #2.

For 72 hours postop, NIRS monitoring. All monitor data collected electronically.

POD #3: Study drug dose #3: EPO 500 units/kg or saline placebo 48 hours after dose #3.

7 days postop: Brain MRI. (pentobarbital IV). Neuro exam before discharge. 3-6 months: Brain MRI immediately before or after 2nd surgery, or as outpatient (IV pentobarb or propofol/midazolam—may use N2O/sevo for induction, cannot intubate if outpatient; OR if cardiac MRI at same time, any indicated anesthetic technique). NIRS x 24h after 2nd surgery.

1,and 3 years: Bayley Scales of Infant Development III. 5 years: Battery of neurodevelopmental tests.

Early primary outcome variable: MRI severity of injury score (decrease by 25%). Late outcome variable Bayley Scales of Infant Development score: improvement by 18% at age 1 years.

Sample size: 60 patients: stratified into 3 groups to give power 0.85, alpha 0.05. Expect to accrue 2-4 patients per month.

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates (<30 days) undergoing cardiac surgery with cardiopulmonary bypass will be enrolled.
  • Inclusion criteria include patients with:

    • single ventricle: hypoplastic left heart syndrome or variant undergoing Norwood Stage I or Sano palliation (SV group);
    • patients with D-transposition of the great vessels with or without ventricular septal defect (VSD) undergoing arterial switch operation with VSD closure if needed (ASO group); and
    • patients with interrupted or hypoplastic aortic arch with intracardiac defects (VSD, ASD, or subaortic stenosis) who are undergoing complete 2- ventricle repair including aortic arch advancement(AAA group), any other 2 ventricle lesion scheduled for complex anatomic repair.

Exclusion Criteria:

  • Gestational age less than 35 weeks at birth
  • Weight less than 2 kg
  • Known recognizable dysmorphic syndrome
  • Surgery not requiring cardiopulmonary bypass
  • Preoperative cardiac arrest requiring chest compressions for greater than 3 minutes
  • Inability to enroll the patient greater than 12 hours preoperatively
  • Aortic crossclamping is not used
  • CPB times are anticipated to be less than 60 minutes
  • A nadir temperature on bypass greater than 25° C is planned.
  • Presence of known contraindications to EPO administration-sustained systolic blood pressure >100, hemoglobin .18 g/dL, known allergy to EPO or one of its components
  • Platelet count >600,000 per dL, INR <0.8.
  • Maternal history of major vascular thrombosis, or multiple fetal loss (3 or more spontaneous abortions).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513240

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
The Dana Foundation
Texas Children's Hospital
Investigators
Principal Investigator: Dean B. Andropoulos, M.D. Baylor College of Medicine/Texas Children's Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Dean Andropoulos, Professor, Chief of Pediatric Anesthesiology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00513240     History of Changes
Other Study ID Numbers: R21HD5550101, FDA IND #100011, Baylor GCRC #0942
Study First Received: August 7, 2007
Results First Received: January 24, 2014
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
erythropoetin
neuroprotection
neonate
cardiac
magnetic resonance imaging
brain magnetic resonance imaging
electroencephalogram

Additional relevant MeSH terms:
Heart Diseases
Transposition of Great Vessels
Heart Defects, Congenital
Hypoplastic Left Heart Syndrome
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014