Overview
In this phase II trial, the investigators overarching goal is to demonstrate the feasibility and potential benefit of darbepoetin (Darbe) plus slow-release intravenous (IV) iron to decrease transfusions, maintain iron sufficiency and improve the neurodevelopmental outcomes of preterm infants.
Investigators hypothesize that in infants < 32 completed weeks of gestation, combined treatment with Darbe plus Ferumoxytol (FMX) or Darbe plus low molecular weight iron dextran (LMW-ID) will: 1) be safe, 2) decrease or eliminate transfusions, 3) maintain iron sufficiency, 4) result in higher hematocrit and 5) improve neurodevelopment. Investigators further hypothesize that when compared to oral iron supplementation (standard care), IV iron will be better tolerated, with less effect on the gastrointestinal (GI) microbiome
Description
Investigators hypothesize that in infants < 32 completed weeks of gestation, combined treatment with Darbe plus FMX or Darbe plus LMW-ID will: 1) be safe, 2) decrease or eliminate transfusions, 3) maintain iron sufficiency, 4) result in higher hematocrit and 5) improve neurodevelopment. Investigators further hypothesize that when compared to oral iron supplementation (standard care), IV iron will be better tolerated, with less effect on the gastrointestinal (GI) microbiome
- Objectives
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- To compare the safety, dose, and dosing interval for FMX and LMW-ID required for preterm infants receiving Darbe.
Iron dosing will begin at 7 days after birth. Initial doses of 10 mg/kg/dose or 20 mg/kg/dose will be compared for each iron formulation (N=20 each).
2. To compare the safety, tolerance, and efficacy of IV iron (FMX or LMW-ID) plus Darbe (N=80) to standard care (oral ferrous sulfate (N=40). Adverse reactions to IV Iron will be documented, as will adverse responses to oral iron (feeding intolerance). Potential differences in the stool microbiome will be evaluated 3 weeks after the initial IV and oral iron doses.
3. Determine long-term outcomes:
- 3.1 Neurodevelopmental outcomes of infants enrolled in Objectives 1 and 2 (N=120) will be sequentially assessed up to 2 years of age.
- 3.2 The stool microbiome will be compared between study groups at 12 and 24 months to determine whether mode of iron delivery has long-term effects.
Eligibility
Inclusion Criteria:
• NICU patients (male and female) born at 24-0/7 to 31-6/7 weeks of gestation
All patients who meet inclusion criteria will be approached without regard to sex, race,
ethnicity, parents' country of origin, or religious preferences.
Exclusion Criteria:
- Known fetal/infant anomalies of clinical significance (brain, cardiac, chromosomal
anomalies)
- Parental consent unable to be obtained by 72 hours after birth
- Central hematocrit > 65%
- Evidence of high iron stores prior to enrollment (e.g. Ferritin >400 ng/mL with
corresponding ZnPP/H of <30, Transferrin saturation >75%, iron > 200 mcg/dL, TIBC <
100 mcg/dL)
- Culture proven sepsis, meningitis, urinary tract infection, or other significant
infection at the time of enrollment
- Mother under 18 years of age
- Unable to consent in English or Spanish