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

NCT ID: NCT05340465

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-27

Study Completion Date

2027-06-30

Brief Summary

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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

Detailed Description

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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.

Conditions

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Prematurity Iron-deficiency Iron Deficiency Anemia Iron Malabsorption

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

* Group 1 Control, oral iron up to 12 mg/kg/day per Unit protocol
* Group 2 Darbe 10 mcg/kg q week plus LMW-ID: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L
* Group 3 Darbe 10 mcg/kg q week plus LMW-ID: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L
* Group 4 Darbe 10 mcg/kg q week plus FMX 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L
* Group 5 Darbe 10 mcg/kg q week plus FMX 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Group 1 will be unblinded. In Groups 2-5 all infants will receive Darbe, and the iron preparation and dose will be blinded.

Study Groups

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Group 1. Oral iron

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.

Group Type ACTIVE_COMPARATOR

Oral iron supplements

Intervention Type DRUG

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).

Group 2

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

Group Type EXPERIMENTAL

Darbepoetin Alfa

Intervention Type DRUG

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 Dextran

Intervention Type DRUG

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.

Group 3

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

Group Type EXPERIMENTAL

Darbepoetin Alfa

Intervention Type DRUG

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 Dextran

Intervention Type DRUG

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.

Group 4

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

Group Type EXPERIMENTAL

Darbepoetin Alfa

Intervention Type DRUG

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

Ferumoxytol injection

Intervention Type DRUG

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.

Group 5

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

Group Type EXPERIMENTAL

Darbepoetin Alfa

Intervention Type DRUG

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

Ferumoxytol injection

Intervention Type DRUG

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.

Interventions

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Darbepoetin Alfa

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

Intervention Type DRUG

Low Molecular Weight Iron Dextran

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.

Intervention Type DRUG

Ferumoxytol injection

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.

Intervention Type DRUG

Oral iron supplements

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).

Intervention Type DRUG

Other Intervention Names

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Aranesp Darbe INFeD LMW-ID Feraheme FMX Ferr-in-sol

Eligibility Criteria

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Inclusion Criteria

• NICU patients (male and female) born at 24-0/7 to 31-6/7 weeks of gestation

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
Maximum Eligible Age

3 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Kendell German

Associate Professor: School of Medicine, Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kendell R German, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kendell R German, MD

Role: CONTACT

(206)221-5716

John Feltner, MS

Role: CONTACT

206 616-8021

Facility Contacts

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John Feltner, MS

Role: primary

206-616-8021

References

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Juul SE, Comstock BA, Mayock DE, German K, Feltner J, Irvine J, Lagerquist E, Heagerty PJ. Darbepoetin plus slow-release IntraVenous Iron to decrease transfusions and improve iron status and neurodevelopment in preterm infants (DIVI): study protocol for a randomized, blinded phase II trial. Trials. 2025 Dec 22;26(1):590. doi: 10.1186/s13063-025-09374-9.

Reference Type DERIVED
PMID: 41430711 (View on PubMed)

Other Identifiers

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R01HD107003

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00015143

Identifier Type: -

Identifier Source: org_study_id

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