Erythropoetin Neuroprotection for Neonatal Cardiac Surgery
Congenital Heart Disease
Hypoplastic Left Heart Syndrome
Transposition of the Great Arteries
Aortic Arch Hypoplasia or Interruption
Drug: Normal saline
|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|
- 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.
- 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 ]
|Study Start Date:||September 2006|
|Estimated Study Completion Date:||September 2016|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Experimental: EPO group
Patients randomized to receive the 3 doses of 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
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
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:
- 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.
- To determine EPO tolerability and safety with short term administration.
- To determine EPO pharmacokinetics in this population.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513240
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Dean B. Andropoulos, M.D.||Baylor College of Medicine/Texas Children's Hospital|