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

NCT05340465 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00015143R01HD107003
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

prematurity; iron deficiency; anemia; darbepoetin; IV Iron

Outcome Measures

Primary Outcomes (4)

• 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

  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

  Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)

• Number of Blood transfusions

  The number of blood transfusions received by infants in each group will be compared.

  Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)

• Volume of blood transfusions

  The volume of blood transfused to infants in each group will be compared

  Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)

Secondary Outcomes (10)

• Number and percent of patients per group that remain transfusion free

  Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)

• Hematocrit

  Birth to 36 weeks PMA

• Safety of IV iron

  Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)

• Early gut microbiome comparison between study groups

  at 7 days (prior to iron supplementation) and 4 weeks after birth

• Rate of referral for Brainstem auditory evoked response

  at hospital discharge, near 36 weeks postmenstrual age

Study Arms (5)

Group 1. Oral iron

ACTIVE COMPARATOR

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.

Drug: Oral iron supplements

Group 2

EXPERIMENTAL

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

Drug: Darbepoetin Alfa; Drug: Low Molecular Weight Iron Dextran

Group 3

EXPERIMENTAL

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

Drug: Darbepoetin Alfa; Drug: Low Molecular Weight Iron Dextran

Group 4

EXPERIMENTAL

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

Drug: Darbepoetin Alfa; Drug: Ferumoxytol injection

Group 5

EXPERIMENTAL

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

Drug: Darbepoetin Alfa; Drug: Ferumoxytol injection

Interventions

Darbepoetin Alfa DRUG

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

Also known as: Aranesp, Darbe

Group 2; Group 3; Group 4; Group 5

Low Molecular Weight Iron Dextran 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.

Also known as: INFeD, LMW-ID

Group 2; Group 3

Ferumoxytol injection 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.

Also known as: Feraheme, FMX

Group 4; Group 5

Oral iron supplements 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).

Also known as: Ferr-in-sol

Group 1. Oral iron

Eligibility Criteria

• Age: Up to 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• University of Washington: lead

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 41430711 DERIVED

MeSH Terms

Conditions

Premature Birth; Anemia, Iron-Deficiency; Iron Deficiencies; Anemia

Interventions

Darbepoetin alfa; Iron-Dextran Complex; Ferrosoferric Oxide

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Study Officials

• Kendell R German, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kendell R German, MD

CONTACT

(206)221-5716; germank@uw.edu

John Feltner, MS

CONTACT

206 616-8021; jfeltner@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Group 1 will be unblinded. In Groups 2-5 all infants will receive Darbe, and the iron preparation and dose will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor: School of Medicine, Pediatrics

Model Details: * 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

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: April 22, 2022
• Study Start: November 27, 2022
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within 12 months of publication of our primary outcome, a final study data set will be accessible via a supervised private data enclave. Access will be limited to registered users who submit proposed specific questions or analysis plans and sign a data use agreement. "Supervised" indicates that individual requests are reviewed to protect the intellectual property rights of the project investigative team by restricting external development of manuscripts using the study data that substantially overlap with those that are already in development by study investigators. We will form a publications committee, with investigator representatives from the Clinical Coordinating Center and Data Coordinating Center at the University of Washington to establish manuscript development and publication guidelines.
• Access Criteria: We will electronically document data requests through a web-based data portal at the University of Washington Center for Biomedical Statistics. The final research data set will be stored separately from the operational study database in a secure web-accessible REDCap database (at https://rcnut.iths.org), where access and downloads can be easily monitored and the data are downloadable in a variety of formats (Excel, R, SAS, Stata, SPSS). A comprehensive data dictionary will be available alongside the final research database. The data sharing plan will be executed within the final year of funding. The overhead required to support this data sharing plan is minimal and therefore no additional budget is requested to cover its costs.

Locations

US (1)