High-Dose Erythropoietin in Extremely Premature Infants to Prevent/Attenuate Brain Injury: A Phase II Study

Sponsor

Atlantic Health System (Other)

Overall Status

Terminated

CT.gov ID

NCT00589953

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The highest risk for perinatal brain injury occurs among extremely premature infants who weigh less than 1250 grams at birth. Such perinatal brain injury is currently irreversible, associated with neurodevelopmental disability, and without adequate treatment modalities. Research in recent years suggest in both animal and human studies that erythropoietin (Epo) may have significant neuroprotective effects. Given the historical safe medical profile of Epo when used for anemia of prematurity but the likely need for a greater dosage regimen for activation of neuroprotective pathways against neonatal brain injury, we therefore propose this phase II study of high-dose Epo in very low birth weight infants for the prevention and/or attenuation of prematurity-related cerebral hemorrhagic-ischemic injury.

Condition or Disease	Intervention/Treatment	Phase
Infant, Premature Erythropoietin Brain Injury Intraventricular Hemorrhage Periventricular Leukomalacia Neurodevelopmental Outcomes Randomized Clinical Trial	Drug: Erythropoietin Drug: Saline placebo	Phase 2

Detailed Description

Eligible extremely premature infants will be enrolled in this double-blind, placebo-controlled randomized trial from the neonatal intensive care unit at Morristown Memorial Hospital (Morristown, New Jersey). Subjects will be enrolled within the first 24 hours of life and randomly assigned to receive Epo or saline vehicle placebo.

Standard NICU care will be provided to all subjects. Serial exams, CBC-d, reticulocyte counts, serum Epo levels, serial HUS, and head MRI will be collected at established time points during the study period. At 18 to 22 months corrected age, subjects will undergo a neurodevelopmental evaluation assessing for cerebral palsy, Bayley Scores of Infant Development-II (BSID-II) Mental Development Index (MDI), BSID-II Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

High-Dose Erythropoietin in Very Low Birth Weight Infants for the Potential Treatment of Prematurity-Related Cerebral Hemorrhagic-Ischemic Injury: A Phase II Safety/Tolerability Study

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: EPO### All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).	Drug: Saline placebo Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life. Other Names: Confidential Randomization Number
Experimental: EPO ### All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).	Drug: Erythropoietin 5 of first 10 subjects (Group 1): 400 units/kg/dose once daily for 7 days 5 of next 10 subjects (Group 2): 800 units/kg/dose once daily for 7 days 20 of next 30 subjects (Group 3): 1000 units/kg/dose once daily for 7 days administered i.v. over 1 hour. The volume of the study drug will be 1 mL in a 1 mL Tuberculin syringe to be administered over 1 hour. Other Names: Confidential Randomization Number

Arm

Intervention/Treatment

Placebo Comparator: EPO###

All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).

Drug: Saline placebo

Saline vehicle at a volume of 1 mL given over 1 hour intravenously once a day for the first seven days of life.

Other Names:

Confidential Randomization Number

Experimental: EPO ###

All subjects will be identified as a such by the study identifier "EPO###" where EPO designates enrollment in this study and ### is a numeric identifier (e.g. 103).

Drug: Erythropoietin

5 of first 10 subjects (Group 1): 400 units/kg/dose once daily for 7 days 5 of next 10 subjects (Group 2): 800 units/kg/dose once daily for 7 days 20 of next 30 subjects (Group 3): 1000 units/kg/dose once daily for 7 days administered i.v. over 1 hour. The volume of the study drug will be 1 mL in a 1 mL Tuberculin syringe to be administered over 1 hour.

Other Names:

Confidential Randomization Number

Outcome Measures

Primary Outcome Measures

Neurodevelopmental evaluations at 18 to 22 months corrected age (cerebral palsy, Bayley Scores of Infant Development Mental Development Index (MDI), Psychomotor Development Index (PDI), bilateral hearing aid use, and visual impairment) [18-22 months corrected age]

Secondary Outcome Measures

Severe intraventricular hemorrhage [First ten days of life]
Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure [NICU hospitalization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 24 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

500 to 1250 grams at birth
Less than 32 weeks gestation at birth
Less than 24 hours of life at time of enrollment

Exclusion Criteria:

Congenital anomalies (chromosomal, CNS, cardiac, GI, pulmonary)
Seizures within first 24 hours of life
Severe neutropenia (ANC < 500 cells/microL) within first 24 hours of life
Polycythemia (Hct > 65%) within first 24 hours of life
Thrombocytopenia (platelets < 50K cells/microL) within first 24 hours of life
Hypertension (SBP > 100mmHg) without vasopressor support within first 24 hours of life