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Completed

NCT Number: NCT03169881

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

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

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Key information

Conditions

Neurocognitive Neonatal Neurodevelopmental Impairment Neuroprotective

Age range

1 hour–24 hour

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Inborn and outborn preterm infants
  • 23 0/7-28 6/7 weeks gestational age
  • ≤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

Treatment and study plan

Darbepoetin

Drug

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.

Other names: Darbe

Placebo

Drug

normal saline for IV administration, or sham dosing. Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.

Other names: normal saline for IV administration, or sham dosing

Primary outcomes

  1. Bayley III Composite Cognitive Score

    Time frame: 22-26 months corrected age (a median of 25 months corrected age, which corresponds to a median of 29 months calendar age in the analysis population), unless the subject died earlier

    Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score, where subjects who died prior to the follow-up assessment are assigned the lowest possible score of 54. This is a standardized scale where a score that is more than 1 normative standard deviation from the normative mean of 100 signifies mild developmental delay (score < 85); 2 standard deviations below the mean, moderate delay (score < 70); and 3 standard deviations below the mean, severe delay (score < 55). This self-standing scale comprises the primary outcome for the Darbe study.

Secondary outcomes

  1. Number of Transfusions Per Infant

    Time frame: Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

    The number of transfusions recorded during the study, up to 35 completed weeks gestational age

  2. Total Volume of Transfusions Per Infant

    Time frame: Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

    The total volume of transfusions for the infant if ever transfused

  3. Number of Donor Exposures Per Infant

    Time frame: Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

    The number of donor exposures recorded during the study, up to 35 completed weeks gestational age

  4. Hematocrit

    Time frame: at 2 and at 7 weeks in the study

    Hematocrit adjusted for center, gestational age group, and familial clustering

  5. Red Cell Mass

    Time frame: at 2 and at 7 weeks in the study

    Red Cell Mass (Circulating Erythrocyte Volume), adjusted for center, gestational age group, and familial clustering

  6. Necrotizing Enterocolitis, Bells Stage >=2 With Surgery

    Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days)

    This is measured as Yes if experienced necrotizing enterocolitis, Bells stage >=2 with surgery; Otherwise, No.

  7. Bronchopulmonary Dysplasia Grades 2 or 3

    Time frame: At 36 weeks postmenstrual age

    This is measured as Yes if infant is on invasive mechanical ventilation, nasal cannula >2 L/min or noninvasive positive airway pressure at 36 weeks of postmenstrual age; Otherwise, No.

  8. Retinopathy of Prematurity Stage >=3 or Treatment for That Condition Received

    Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days)

    This is measured as Yes if experienced Retinopathy of prematurity stage >=3 or treatment for that condition received; Otherwise, No. Higher stages of ROP indicate a worse outcome; the stages range from 1 for "mild" disease, to 5 for "severe" disease.

  9. Intraventricular Hemorrhage Grade I+

    Time frame: Birth to initial hospital discharge or to death if it occurs earlier (a median of 94 days)

    This is measured as Yes if experienced Grade I+ Intraventricular Hemorrhage; Otherwise, No.

  10. Length of Hospital Stay

    Time frame: At initial hospital discharge or at death if it occurs earlier (a median of 94 days), assessed up to one year of life.

    This is measured as the length of stay up to hospital discharge or death, whichever occurred first.

  11. Death

    Time frame: Birth, through the 22-26 months corrected age follow-up window, which corresponds to a median of 29 months calendar age in the analysis population

    This is measured as Yes if an infant died between birth and 22-26 months corrected age; Otherwise, No.

  12. Neurodevelopmental Impairment

    Time frame: At 22-26 months corrected age (a median of 25 months corrected age)

    This is a 4-level outcome, where Severe NDI denotes a BSID III cognitive score less than 70, a Gross Motor Functional (GMF) level of 3-5 (where higher scores indicate worse outcomes), blindness (less than 20/200 vision), and/or profound hearing loss, Moderate NDI denotes a BSID III cognitive score from 70-84 and either a GMF level of 2 or limited blindness / moderate hearing loss, Mild NDI denotes a BSID III cognitive score from 70-84, or a cognitive score >=85 with a GMF level of 1 and/or mild hearing loss, and No NDI denotes a cognitive score >= 85 and an absence of neurosensory deficits.

  13. Any Cerebral Palsy

    Time frame: At 22-26 months corrected age (a median of 25 months corrected age)

    This is measured as Yes if the child has been deemed by the medical examiner as having Cerebral Palsy; Otherwise, No.

Sponsors and collaborators

Lead sponsor

NICHD Neonatal Research Network

Network

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: Darbe

Important dates

Study start
2017
Primary completion
2022
Study completion
2025
First posted
May 30, 2017
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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