Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants

Neonatal Clinical Trial

— Darbe  

Official title:

Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03169881
• Other study ID #: NICHD-NRN-0058
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 20, 2017
• Est. completion date: August 2028

Study information

• Verified date: December 2023
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study Hypothesis: Preterm infants administered weekly Darbe during the neonatal period will have improved neurocognitive outcome at 22-26 months compared to placebo

Description:

Advances in neonatal care have led to significant improvements in the survival of the nearly 60,000 very low birth weight (VLBW) infants born each year in the U.S. Improving neurodevelopmental outcomes for these preterm infants continues to be a major goal for neonatal care providers. A subset of these infants sustain a grade 3 or 4 intraventricular hemorrhage (IVH) resulting in an increase in the incidence of developmental delay. Moreover, almost one third of preterm infants with normal head ultrasounds also develop cognitive delay. Although a variety of neuroprotective treatment strategies have been evaluated, no specific treatment has been identified to reduce or prevent brain injury in these most vulnerable preterm infants.

A potential neuroprotective therapy involves administering erythropoiesis stimulating agents (ESAs) such as erythropoietin (Epo) and Darbepoetin (Darbe, a longer acting ESA). In addition to stimulating erythropoiesis, ESAs have been shown to be protective in the developing brain in animal models, making it possibly beneficial for very premature infants who are at risk for intraventricular hemorrhage, hypoxic-ischemic injury, and developmental delay. The neuroprotective mechanisms of ESAs include increased neurogenesis, decreased neuronal susceptibility to glutamate toxicity, decreased neuronal apoptosis, decreased inflammation, decreased nitric oxide-mediated injury, increased antioxidant response, decreased axonal degeneration, and increased protective effects on glia. This is a randomized, masked, placebo controlled clinical study in which enrolled infants will receive weekly Darbe or placebo (sham) dosing.

Extended follow-up: Subjects will be seen for follow-up at 4-5 years (i.e., 4 years - 4 years 11 months) corrected age and 6-7 years (i.e., 6 years - 6 years 11 months) corrected age to characterize the functional, behavioral and neurological outcomes of the extremely low birth weight (ELBW) population at school age based on treatment with darbepoetin versus placebo in the neonatal period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 650
• Est. completion date: August 2028
• Est. primary completion date: December 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 28 Weeks

Eligibility

Inclusion Criteria:

• Inborn and outborn preterm infants

• 23 0/7-28 6/7 weeks gestation

• =24 hours postnatal age

Exclusion Criteria:

• Hematocrit > 60%

• Infants with known congenital or chromosomal anomalies, including congenital heart disease and known brain anomalies

• Hemorrhagic or hemolytic disease

• EEG- confirmed seizures

• Congenital thrombotic disease

• Systolic blood pressures >100 mm Hg while not on pressor support

• Receiving Epo or Darbe clinically, or planning to receive Epo or Darbe during hospitalization

• Infants in whom no aggressive therapy is planned

• Family will NOT be available for follow-up at 22-26 months

Related Conditions & MeSH terms

• Neonatal
• Neurocognitive
• Neurodevelopmental Impairment
• Neuroprotective

Intervention

Drug:
• Darbepoetin
Darbepoetin 10 micrograms/kg/once every week (IV or SC). Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.
• Placebo
normal saline for IV administration, or sham dosing. Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Stanford University	Palo Alto	California
United States	Univeristy of Pennsylvania	Philadelphia	Pennsylvania
United States	Brown University - Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite cognitive score on Bayley Scale of Infant Development III	The primary outcome is the Bayley III cognitive score. Deaths will be assigned a score of 54.	Birth to 26 months corrected age
Secondary	Death	Death includes any mortality prior to follow-up at 22-26 months of age	Birth to 26 months corrected age
Secondary	Cerebral Palsy		Follow-up at 26 months corrected age
Secondary	Length of Hospital Stay	Days in hospital following birth.	Birth to 26 months corrected age
Secondary	Number of transfusions		Birth to 35 completed weeks gestational age
Secondary	Hematocrit		Birth to 35 completed weeks gestational age
Secondary	Red cell mass		Birth to 35 completed weeks gestational age
Secondary	Volume of transfusions		Birth to 35 completed weeks gestational age
Secondary	Neurodevelopmental impairment (NDI)	Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score = 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score = 85 and absence of any neurosensory deficits.	26 months corrected age
Secondary	Seizures	Documented seizures during hospital course	Up to 120 days of life
Secondary	Thromboses	Documented thromboses during hospital course	Up to 120 days of life
Secondary	Hypertension	Documented hypertension during hospital course	Up to 120 days of life
Secondary	Intra-cranial Hemorrhage (ICH)	Documented ICH during hospital course	Up to 120 days of life
Secondary	Necrotizing Enterocolitis (NEC) requiring surgery	Documented NEC requiring surgery during hospital course	Up to 120 days of life
Secondary	Bronchopulmonary dysplasia (BPD)	Documented BPD during hospital course	Up to 120 days of life
Secondary	Retinopathy of prematurity (ROP) requiring intervention	Documented ROP requiring intervention (to include but not limited to laser, cryotherapy, scleral buckle, vitrectomy, avastin Injection) during hospital course	Up to 120 days of life
Secondary	Culture positive sepsis	Documented culture positive sepsis during hospital course	Up to 120 days of life