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Erythropoetin Neuroprotection for Neonatal Cardiac Surgery

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ClinicalTrials.gov Identifier: NCT00513240
Recruitment Status : Unknown
Verified November 2016 by Dean Andropoulos, Baylor College of Medicine.
Recruitment status was:  Active, not recruiting
First Posted : August 8, 2007
Results First Posted : May 19, 2014
Last Update Posted : January 6, 2017
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Dana Foundation
Texas Children's Hospital
Information provided by (Responsible Party):
Dean Andropoulos, Baylor College of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Prevention
Conditions Congenital Heart Disease
Hypoplastic Left Heart Syndrome
Transposition of the Great Arteries
Aortic Arch Hypoplasia or Interruption
Interventions Drug: Erythropoetin
Drug: Normal saline
Enrollment 62

Recruitment Details Subjects recruited from September 2006 to February 2011 in the Texas Children's Hospital Heart Center NICU and CVICU.
Pre-assignment Details 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.
Arm/Group Title EPO Group Control Group.
Hide Arm/Group Description

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

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.

Period Title: Overall Study
Started 35 [1] 27 [2]
Clinical Data Collection &Pre/Postop MRI 32 [3] 27
Completed 22 [4] 20 [4]
Not Completed 13 7
Reason Not Completed
Did not have intended surgery             3             0
Death             3             3
Withdrawal by Subject             7             4
[1]
3 did not have intended surgery; 28 had all 3 doses; 4 had 1 dose but no more due to delayed surgery
[2]
25 had 3 doses; 1 had 1 dose due to rash; 1 had 2 doses and 1 dose of EPO due to pharmacy error
[3]
3 not having intended surgery are subtracted from original 35 subjects, leaving 32
[4]
Competed 12 month neurodevelopmental exam, which are the only results published at this time.
Arm/Group Title EPO Group Control Group. Total
Hide Arm/Group Description

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

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 of all reporting groups
Overall Number of Baseline Participants 32 27 59
Hide Baseline Analysis Population Description
These were the number of subjects followed for the intention-to-treat analysis because they received at least one dose of study drug/placebo.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 32 participants 27 participants 59 participants
8.94  (5.35) 8.12  (4.09) 8.58  (4.85)
[1]
Measure Description: Age at inclusion surgery
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 27 participants 59 participants
Female
16
  50.0%
11
  40.7%
27
  45.8%
Male
16
  50.0%
16
  59.3%
32
  54.2%
Cardiac diagnosis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants 27 participants 59 participants
Hypoplastic Left Heart Syndrome (HLHS) 16 10 26
(D-Transposition of the Great Arteries (D-TGA) 9 12 21
Aortic Arch & Ventricular Septal Defect/Other 7 5 12
Any preoperative MRI injury  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants 27 participants 59 participants
Injury 13 9 22
No Injury 19 18 37
New postoperative MRI injury  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants 27 participants 59 participants
Injury 13 13 26
No Injury 19 14 33
1.Primary Outcome
Title MRI Severity of Injury Score
Hide Description 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.
Time Frame 7 days postoperatively.
Outcome Measure Data Not Reported
2.Primary Outcome
Title Scores on Bayley Scales of Infant Development III at Age 1 Years.
Hide Description 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.
Time Frame 1 year postoperatively
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EPO 1000 Units/kg QDx3 EPO 500 Units/kg QODx3 Placebo
Hide Arm/Group Description:
Original dose of 1000 units/kg every day for 3 doses
Revised dose after FDA clinical hold removed of EPO 500 units/kg every other day for 3 doses
Placebo
Overall Number of Participants Analyzed 11 11 20
Mean (Standard Deviation)
Unit of Measure: units on a scale
12-Month BSID-III Cognitive 101.4  (16.9) 100.9  (10.2) 106.3  (10.7)
12-Month BSID-III Language 85.0  (16.3) 92.0  (7.3) 92.4  (12.4)
12-Month BSID-III Motor 89.3  (15.7) 90.5  (8.6) 92.6  (14.1)
3.Secondary Outcome
Title EEG Seizure Burden in the First 72 Postoperative Hours. (Total Minutes of EEG Seizures).
Hide Description [Not Specified]
Time Frame 72 hours postoperatively.
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Pharmacokinetics of High Dose Erythropoetin: 7 Erythropoetin Levels in First 24 Hours After First Dose.
Hide Description [Not Specified]
Time Frame 24 hours after first EPO dose.
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title EPO Group Control Group.
Hide Arm/Group Description

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

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.

All-Cause Mortality
EPO Group Control Group.
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
EPO Group Control Group.
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/35 (0.00%)      0/27 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
EPO Group Control Group.
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/35 (11.43%)      3/27 (11.11%)    
Cardiac disorders     
Postop ECMO  [1]  1/35 (2.86%)  1 0/27 (0.00%)  0
Nervous system disorders     
Postoperative dural sinovenous thrombosis  [2]  3/35 (8.57%)  3 3/27 (11.11%)  3
Clinical seizures  [3]  1/35 (2.86%)  1 0/27 (0.00%)  0
New cerebral infarction adjuacent to thrombosis on postop MRI  [4]  1/35 (2.86%)  1 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Cardiac arrest and subsequent ECMO
[2]
As evidenced by MRI exam
[3]
Clinical seizures diagnosed by physician exam
[4]
New cerebral infarction adjuacent to thrombosis on postop MRI
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Dean B. Andropoulos
Organization: Baylor College of Medicine
Phone: 832-826-5831
EMail: dra@bcm.edu
Other Publications:
Responsible Party: Dean Andropoulos, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00513240     History of Changes
Other Study ID Numbers: R21HD5550101
FDA IND #100011
Baylor GCRC #0942
First Submitted: August 7, 2007
First Posted: August 8, 2007
Results First Submitted: January 24, 2014
Results First Posted: May 19, 2014
Last Update Posted: January 6, 2017