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

University of Washington

Status and phase: Enrolling; Phase 2

Conditions: Iron Deficiency Anemia; Iron-deficiency; Prematurity; Iron Malabsorption

Treatments: Drug: Low Molecular Weight Iron Dextran; Drug: Ferumoxytol injection; Drug: Darbepoetin Alfa; Drug: Oral iron supplements

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05340465

STUDY00015143

R01HD107003 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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:

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.

Enrollment: 120 estimated patients

Sex: All

Ages: Under 3 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 5 patient groups

Group 1. Oral iron

Active Comparator group

Description:

Oral iron is started on day 7 of life if baby is feeding 100 mL/kg/day. Iron supplements of up to 12 mg/kg/day are given based on CBC, retic, ret-hgb, serum ferritin and zinc protoporphyrin to heme ratio (ZnPP/H). Iron supplements are adjusted every 2 weeks following iron studies.

Treatment:

Drug: Oral iron supplements

Group 2

Experimental group

Description:

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Treatment:

Drug: Darbepoetin Alfa

Drug: Low Molecular Weight Iron Dextran

Group 3

Experimental group

Description:

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Treatment:

Drug: Darbepoetin Alfa

Drug: Low Molecular Weight Iron Dextran

Group 4

Experimental group

Description:

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Treatment:

Drug: Darbepoetin Alfa

Drug: Ferumoxytol injection

Group 5

Experimental group

Description:

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Treatment:

Drug: Darbepoetin Alfa

Drug: Ferumoxytol injection