Trial Outcomes & Findings for Erythropoetin Neuroprotection for Neonatal Cardiac Surgery (NCT NCT00513240)
NCT ID: NCT00513240
Last Updated: 2020-02-07
Results Overview
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.
COMPLETED
PHASE1/PHASE2
62 participants
7 days postoperatively.
2020-02-07
Participant Flow
Subjects recruited from September 2006 to February 2011 in the Texas Children's Hospital Heart Center NICU and CVICU.
357 assessed for eligibility; 253 did not meet inclusion criteria. 42 subjects that eligible but consent not obtained (24 declined, 2 enrolled in another study, 16 investigator not available for consent or patient lived too far away). 62 consented, enrolled, received 1 dose EPO, but intended surgery not done on 3 subjects (no CPB); leaving 59.
Participant milestones
| Measure |
EPO Group
Patients randomized to receive the 3 doses of erythropoetin.
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
|
Control Group.
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
27
|
|
Overall Study
Clinical Data Collection &Pre/Postop MRI
|
32
|
27
|
|
Overall Study
COMPLETED
|
22
|
20
|
|
Overall Study
NOT COMPLETED
|
13
|
7
|
Reasons for withdrawal
| Measure |
EPO Group
Patients randomized to receive the 3 doses of erythropoetin.
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
|
Control Group.
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
|---|---|---|
|
Overall Study
Did not have intended surgery
|
3
|
0
|
|
Overall Study
Death
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
7
|
4
|
Baseline Characteristics
Erythropoetin Neuroprotection for Neonatal Cardiac Surgery
Baseline characteristics by cohort
| Measure |
EPO Group
n=32 Participants
Patients randomized to receive the 3 doses of erythropoetin.
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
|
Control Group.
n=27 Participants
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
8.94 days
STANDARD_DEVIATION 5.35 • n=5 Participants
|
8.12 days
STANDARD_DEVIATION 4.09 • n=7 Participants
|
8.58 days
STANDARD_DEVIATION 4.85 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Cardiac diagnosis
Hypoplastic Left Heart Syndrome (HLHS)
|
16 participants
n=5 Participants
|
10 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Cardiac diagnosis
(D-Transposition of the Great Arteries (D-TGA)
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Cardiac diagnosis
Aortic Arch & Ventricular Septal Defect/Other
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Any preoperative MRI injury
Injury
|
13 participants
n=5 Participants
|
9 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Any preoperative MRI injury
No Injury
|
19 participants
n=5 Participants
|
18 participants
n=7 Participants
|
37 participants
n=5 Participants
|
|
New postoperative MRI injury
Injury
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
New postoperative MRI injury
No Injury
|
19 participants
n=5 Participants
|
14 participants
n=7 Participants
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 days postoperatively.Population: Preoperative and postoperative MRIs were available to be scored on 33 subjects.
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.
Outcome measures
| Measure |
EPO Group
n=17 Participants
Patients randomized to receive the 3 doses of erythropoetin.
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 Group
n=16 Participants
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
Placebo
Normal saline control
|
|---|---|---|---|
|
Relative Difference in Total Maturity Score (TMS) From Preoperative Brain MRI to 7 Day Postoperative MRI
|
12.1 Percentage
Interval 0.0 to 37.5
|
9.44 Percentage
Interval 0.0 to 30.0
|
—
|
PRIMARY outcome
Timeframe: 1 year postoperatively3 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.
Outcome measures
| Measure |
EPO Group
n=11 Participants
Patients randomized to receive the 3 doses of erythropoetin.
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 Group
n=11 Participants
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
Placebo
n=20 Participants
Normal saline control
|
|---|---|---|---|
|
Scores on Bayley Scales of Infant Development III at Age 1 Years.
12-Month BSID-III Cognitive
|
101.4 units on a scale
Standard Deviation 16.9
|
100.9 units on a scale
Standard Deviation 10.2
|
106.3 units on a scale
Standard Deviation 10.7
|
|
Scores on Bayley Scales of Infant Development III at Age 1 Years.
12-Month BSID-III Language
|
85.0 units on a scale
Standard Deviation 16.3
|
92.0 units on a scale
Standard Deviation 7.3
|
92.4 units on a scale
Standard Deviation 12.4
|
|
Scores on Bayley Scales of Infant Development III at Age 1 Years.
12-Month BSID-III Motor
|
89.3 units on a scale
Standard Deviation 15.7
|
90.5 units on a scale
Standard Deviation 8.6
|
92.6 units on a scale
Standard Deviation 14.1
|
SECONDARY outcome
Timeframe: 72 hours postoperatively.Outcome measures
| Measure |
EPO Group
n=32 Participants
Patients randomized to receive the 3 doses of erythropoetin.
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 Group
n=27 Participants
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
Placebo
Normal saline control
|
|---|---|---|---|
|
EEG Seizure Burden in the First 72 Postoperative Hours. (Total Minutes of EEG Seizures).
|
0 minutes
Interval 0.0 to 0.0
|
0 minutes
Interval 0.0 to 0.0
|
—
|
SECONDARY outcome
Timeframe: 24 hours after first EPO dose.Population: Three patients had pharmacokinetic data obtained; 1 placebo and 2 patients who received EPO 1000 units/kg. Pharmacokinetic modeling was not performed because of these small patient numbers; however, maximum EPO plasma concentrations were measured in the EPO group. Outcome does not apply to the Placebo group and as such they were not analyzed.
Outcome measures
| Measure |
EPO Group
n=2 Participants
Patients randomized to receive the 3 doses of erythropoetin.
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 Group
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
Placebo
Normal saline control
|
|---|---|---|---|
|
Pharmacokinetics of High Dose Erythropoetin: 7 Erythropoetin Levels in First 24 Hours After First Dose (Maximum EPO Plasma Concentration)
|
6931 mIU/mL
Interval 5447.0 to 8415.0
|
—
|
—
|
Adverse Events
EPO Group
Control Group.
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
EPO Group
n=35 participants at risk
Patients randomized to receive the 3 doses of erythropoetin.
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
|
Control Group.
n=27 participants at risk
Patients randomized to receive 3 doses of normal saline control.
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.
.
|
|---|---|---|
|
Nervous system disorders
Postoperative dural sinovenous thrombosis
|
8.6%
3/35 • Number of events 3
|
11.1%
3/27 • Number of events 3
|
|
Nervous system disorders
Clinical seizures
|
2.9%
1/35 • Number of events 1
|
0.00%
0/27
|
|
Nervous system disorders
New cerebral infarction adjacent to thrombosis on postop MRI
|
2.9%
1/35 • Number of events 1
|
0.00%
0/27
|
|
Cardiac disorders
Postop ECMO
|
2.9%
1/35 • Number of events 1
|
0.00%
0/27
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place