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

Brain Injury Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00589953
• Other study ID #: R06-04-004
• Secondary ID: IND12537
• Status: Terminated
• Phase: Phase 2
• First received: December 27, 2007
• Last updated: July 29, 2013
• Start date: July 2007
• Est. completion date: September 2010

Study information

• Verified date: July 2013
• Source: Atlantic Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injury
• Cerebral Hemorrhage
• Erythropoietin
• Hemorrhage
• Infant, Premature
• Intraventricular Hemorrhage
• Leukomalacia, Periventricular
• Neurodevelopmental Outcomes
• Periventricular Leukomalacia
• Premature Birth
• Randomized Clinical Trial
• Wounds and Injuries

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Morristown Medical Center	Morristown	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Atlantic Health System

Country where clinical trial is conducted

United States, 

References & Publications (25)

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Sola A, Rogido M, Lee BH, Genetta T, Wen TC. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatr Res. 2005 Apr;57(4):481-7. Epub 2005 Feb 17. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Severe intraventricular hemorrhage		First ten days of life
Secondary	Polycythemia, neutropenia, thrombocytopenia, hypertension, sepsis, hemorrhage, seizure		NICU hospitalization