Darbe Plus IV Iron to Decrease Transfusions While Maintaining Iron Sufficiency in Preterm Infants

Phase 2RecruitingNCT05340465

University of Washington120 enrolled

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

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: 1. 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

Darbepoetin AlfaDRUG

Infants in groups 2-5 will be started on Darbe 10 mcg/kg/week between 72 and 84 hours after birth.

Low Molecular Weight Iron DextranDRUG

Infants in groups 2 and 3 will be given LMW-ID IV, 10 or 20 mg/kg/dose. They will be re-dosed if ferritin falls below 76. Iron parameters will be checked biweekly.

Ferumoxytol injectionDRUG

Infants in groups 4 and 5 will be given FMX IV, 10 or 20 mg/kg/dose. They will be re-dosed if ferritin falls below 76. Iron parameters will be checked biweekly.

Oral iron supplementsDRUG

Infants in group 1 will receive standard care in the UW NICU with iron started on day 7 if tolerating 100 mL/kg/day enteral feeding. Iron supplements are adjusted every 2 weeks based on ferritin, zinc protoporphyrin to heme ratio and complete blood count (CBC).

Eligibility

Sex: ALLMax age: 3 Days

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Plasma Ferritin at 35-36 weeks PMA

Plasma ferritin is measured every 2 weeks in the NICU. Ferritin at 35-36 weeks will be compared between the 5 treatment groups

Time frame: birth to 36 weeks postmenstrual age

Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL

Number of IV iron doses required to maintain a ferritin level of \> 75 ng/mL will be compared in the 4 IV treatment arms