Erythropoetin Neuroprotection for Neonatal Cardiac Surgery
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Peripheral Vascular Disease, Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/21/2016 |
| Start Date: | September 2006 |
| End Date: | September 2016 |
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.
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.
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.
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.
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).
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