Iron Supplementation and Neurodevelopmental Outcome in ELGANs

NCT04691843 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 2021-4092
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores the relationship between iron deficiency and neurological outcome of extremely premature infants. Premature birth occurs during a critical period of brain development and maturation, and before adequate transfer of iron across the placenta. Nutrition has a significant impact on ultimate outcome of survivors of prematurity. One of the biomarkers of nutrition in the premature infant is iron, and iron supplementation is essential for growth and brain development at low gestational age. As a result, the Committee on Nutrition of the American Academy of Pediatrics (AAP) recommends daily oral iron supplementation, of at least 2-4 mg/kg/day from 2 weeks of age, to prevent iron deficiency in extremely premature infants. Nevertheless, studies have shown that even with this regular care dose of iron, started from 2 weeks of age, a significant number of premature infants will still develop iron-deficiency. Our hypothesis states that starting high dose iron supplementation early will improve neurological development and outcome in extremely premature infants (those born at less than 28 weeks gestational age). This study will provide data showing whether individualized iron supplementation using higher doses of iron, started earlier (after the first week of life) when guided by periodic screening of their body's iron status with ferritin levels, will mitigate iron deficiency and promote improved neurodevelopmental outcome in this vulnerable infant population.

Conditions

Iron-deficiency

Keywords

extreme prematurity; neurodevelopmental impairment; ferritin

Outcome Measures

Primary Outcomes (1)

• Neurodevelopmental outcome in participants

  ND impairment (NDI): defined as the presence of any of the following: Bayley Scales of Development III Motor Standard Score, Language or Cognitive Standard Score \< 70 (severe, 2 standard deviations (SD) below mean) or \< 85 (moderate, 1 SD below mean)

  22-26 months corrected age

Secondary Outcomes (4)

• Iron insufficiency as assessed by ferritin level (ng/mL)

  At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks

• Iron insufficiency as assessed by hemoglobin level (g/dL)

  At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks

• Iron insufficiency as assessed by reticulocyte hemoglobin equivalent (Ret-He, pg)

  At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks

• Iron insufficiency as assessed by reticulocyte count (%)

  At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks

Other Outcomes (2)

• Assess whether measurement of ferritin (ng/mL) or hemoglobin (g/dL) is superior in guiding intervention of iron-insufficiency

  Throughout hospitalization, up to 16 weeks

• Assess whether measurement of ferritin (ng/mL) or reticulocyte count (%) is superior in guiding intervention of iron-insufficiency

  Throughout hospitalization, up to 16 weeks

Study Arms (2)

Standard iron dose

ACTIVE COMPARATOR

Iron supplementation of 4mg/kg/day will start when infant is on full enteral feedings of 120-150mL/kg/day and at least two weeks old. Iron dosing will be adjusted for weight at weekly intervals to maintain dosing at 4mg/kg/day.

Drug: Iron Sulfate

Early, high-dose iron

EXPERIMENTAL

Iron supplementation will start at 3mg/kg/day when infant is on enteral feeds of 60mL/kg/day and at least one week old, then increased to 6mg/kg/day when enteral feeds are at 100mL/kg/day. Iron dosing will be adjusted to maintain ferritin level of 70-400ng/mL. At 36 weeks corrected age, iron supplementation will be adjusted to the dose routinely used for preterm infants.

Drug: Iron Sulfate

Interventions

Iron Sulfate DRUG

Early, high dose, iron supplementation

Also known as: Ferrous Sulfate

Early, high-dose iron; Standard iron dose

Eligibility Criteria

• Age: 7 Days - 4 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• NICU inpatients between 24-0/7 and 30-6/7 weeks of gestation
• Infants older than one week of age and tolerating at least 60ml/kg/day of enteral feeds.
• Parental permission obtained prior to start of study

You may not qualify if:

• In extremis during consent window (as judged by primary attending provider)
• Known or suspected genetic disorder
• Unable to return for follow-up evaluation at 2 years of age

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead

Study Sites (1)

Prentice Women's Hospital

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency

Interventions

Iron-Dextran Complex; ferrous sulfate

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Janine Y Khan, MD, MBA

  Ann & Robert H Lurie Children's Hospital of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Neonatologist

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 31, 2020
• Study Start: February 1, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)