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NCT Number: NCT05340465

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

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

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Key information

Conditions

Prematurity Anemia Anemia, Hypochromic Anemia, Iron-Deficiency Female Urogenital Diseases and Pregnancy Complications Hematologic Diseases Hemic and Lymphatic Diseases Iron Deficiencies Iron Deficiency Anemia Iron Malabsorption Iron Metabolism Disorders Iron-deficiency Metabolic Diseases Nutritional and Metabolic Diseases Obstetric Labor Complications Obstetric Labor, Premature Pregnancy Complications Premature Birth Urogenital Diseases

Age range

Up to 3 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Washington

Seattle, Washington, 98195, United States

Location status: Recruiting

Location contact

Dennis E Mayock, MD

SUB_INVESTIGATOR

John Feltner, MS

CONTACT

[email protected]

206 616-8021

Katie Strobel, MD

SUB_INVESTIGATOR

Kendell R German, MD

PRINCIPAL_INVESTIGATOR

Sandra E Juul, MD, PhD

SUB_INVESTIGATOR

Sara Neches, MD

SUB_INVESTIGATOR

Sarah Kolnik, MD

SUB_INVESTIGATOR

About this study

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:

  • 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).

  • 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.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

darbepoetin alfa

Drug

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

Other names: Aranesp, Darbe

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.

Other names: INFeD, LMW-ID

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.

Other names: Feraheme, FMX

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).

Other names: Ferr-in-sol

Primary outcomes

  1. Plasma Ferritin at 35-36 weeks PMA

    Time frame: birth to 36 weeks postmenstrual age

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

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

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

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

  3. Number of Blood transfusions

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

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

  4. Volume of blood transfusions

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

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

Secondary outcomes

  1. Number and percent of patients per group that remain transfusion free

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

    Number and percent of patients per group that remain transfusion free will be compared by group

  2. Hematocrit

    Time frame: Birth to 36 weeks PMA

    Hematocrit (lowest, highest, mean) by group to 35-36 weeks PMA

  3. Safety of IV iron

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

    Any evidence of anaphylaxis will be documented during and after the first IV infusion of iron

  4. Early gut microbiome comparison between study groups

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

    Stool samples will be collected for 16S amplicon sequencing and targeted culturomics. Organism types will be compared between groups prior to and 3 weeks after the first IV iron dose.

  5. Rate of referral for Brainstem auditory evoked response

    Time frame: at hospital discharge, near 36 weeks postmenstrual age

    Any latency in Brainstem auditory evoked response will be assessed and compared between study arms

  6. Rate of pass/fail the General Movements Assessments (GMA)

    Time frame: 3 months corrected age

    General Movements Assessments (GMA) will be assessed at 3 months corrected age, and results compared between study arms.

  7. Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups

    Time frame: 6 months corrected age

    Parent questionnaire (WIDEA-FS) to assess neurodevelopment will be done at 6 months corrected age. Mean and median scores will be compared by treatment arm. The WIDEA includes 50 items with a maximum score of 200. Higher scores indicate more advanced neurodevelopmental functioning.

  8. Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups

    Time frame: 18 months corrected age

    Parent questionnaire (WIDEA-FS) to assess neurodevelopment will be done at 6 months corrected age. Mean and median scores will be compared by treatment arm. The WIDEA includes 50 items with a maximum score of 200. Higher scores indicate more advanced neurodevelopmental functioning.

  9. Late gut microbiome comparison between study groups

    Time frame: at 1 and 2 years corrected age.

    Stool samples will be collected for 16S amplicon sequencing and targeted culturomics. Organism types will be compared between groups. If differences in early microbiome (at 4 weeks of age) are noted, we will evaluate whether they persist at 1 and 2 years of age.

  10. Neurodevelopmental outcome as assessed by the Bayley Scales of Infant Development edition-IV (BSID-IV)

    Time frame: 1 year and 2 years corrected age

    Bayley Scales of Infant Development edition-IV (BSID-IV) will be assessed in all enrolled patients at one and two years corrected age. Results for the treatment arms will be compared.

Study contacts

Contact information is provided by the study sponsor or research team.

John Feltner, MS

CONTACT

[email protected]

206 616-8021

Kendell R German, MD

CONTACT

[email protected]

(206)221-5716

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Collaborators

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

Registry information

Official study title

Trial of Darbepoetin Plus Slow-release Intravenous Iron to Decrease Transfusions and Improve Iron Status and Neurodevelopment in Preterm Infants

Acronym: DIVI

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Apr 22, 2022
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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