Erythropoetin Neuroprotection for Neonatal Cardiac Surgery
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00513240 |
|
Recruitment Status :
Completed
First Posted : August 8, 2007
Results First Posted : May 19, 2014
Last Update Posted : February 7, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | 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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 62 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | Erythropoetin Neuroprotection for Neonatal Cardiac Surgery |
| Study Start Date : | September 2006 |
| Actual Primary Completion Date : | September 2012 |
| Actual Study Completion Date : | September 2015 |
| Arm | Intervention/treatment |
|---|---|
|
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:
|
|
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 |
- Relative Difference in Total Maturity Score (TMS) From Preoperative Brain MRI to 7 Day Postoperative MRI [ Time Frame: 7 days postoperatively. ]
TMS is a measure of developmental maturity of the brain as assessed from T1 and T2-weighted images, grading myelination, cortical infolding, involution of the germinal matrix, and presence of bands of migrating glial cells. The brain MRIs were reviewed for infarction, hemorrhage, white matter injury (WMI), or dural sinovenous thrombosis (DVST). Injuries in each category are scored 0 for none, 1 for mild, 2 for moderate, 3 for severe. The score in each category is then multiplied by a proposed outcome significance multiplier. A total injury score of 0 signifies no injury, 1-5 a mild injury, 6-10 a moderate injury, and >10 a severe injury. Range of scores is 0 - 51. Lower scores indicate less injury.
The results present the relative difference of this score between the pre- and post-operative MRI. This was calculated as ((Post-operative MRI TMS - Pre-operative MRI TMS) / (Absolute(Pre-operative MRI TMS)) ). The proportion is then converted into a percentage.
- Scores on Bayley Scales of Infant Development III at Age 1 Years. [ Time Frame: 1 year postoperatively ]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. ]
- Pharmacokinetics of High Dose Erythropoetin: 7 Erythropoetin Levels in First 24 Hours After First Dose (Maximum EPO Plasma Concentration) [ Time Frame: 24 hours after first EPO dose. ]
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, Learn About Clinical Studies.
| Ages Eligible for Study: | up to 30 Days (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
Publications of Results:
Other Publications:
| Responsible Party: | Dean Andropoulos, Professor, Chief of Pediatric Anesthesiology, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00513240 |
| Other Study ID Numbers: |
R21HD5550101 IND #100011 ( Other Identifier: FDA ) 0942 ( Other Grant/Funding Number: Baylor College of Medicine General Clinical Research Center ) 1R21HD055501-01 ( U.S. NIH Grant/Contract ) Not Assigned ( Other Grant/Funding Number: Charles A. Dana Foundation Brain and Immuno-Imaging Grant ) |
| First Posted: | August 8, 2007 Key Record Dates |
| Results First Posted: | May 19, 2014 |
| Last Update Posted: | February 7, 2020 |
| Last Verified: | January 2020 |
|
erythropoetin neuroprotection neonate cardiac |
magnetic resonance imaging brain magnetic resonance imaging electroencephalogram |
|
Heart Diseases Hypoplastic Left Heart Syndrome Transposition of Great Vessels Cardiovascular Diseases Heart Defects, Congenital |
Cardiovascular Abnormalities Congenital Abnormalities Epoetin Alfa Hematinics |