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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Plasma Ferritin at 35-36 weeks PMA [Срок оценки: birth to 36 weeks postmenstrual age]
• Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL [Срок оценки: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)]
• Number of Blood transfusions [Срок оценки: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)]
• Volume of blood transfusions [Срок оценки: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)]

Вторичные конечные точки (10)

• Number and percent of patients per group that remain transfusion free [Срок оценки: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)]
• Hematocrit [Срок оценки: Birth to 36 weeks PMA]
• Safety of IV iron [Срок оценки: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)]
• Early gut microbiome comparison between study groups [Срок оценки: at 7 days (prior to iron supplementation) and 4 weeks after birth]
• Rate of referral for Brainstem auditory evoked response [Срок оценки: at hospital discharge, near 36 weeks postmenstrual age]
• Rate of pass/fail the General Movements Assessments (GMA) [Срок оценки: 3 months corrected age]
• Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups [Срок оценки: 6 months corrected age]
• Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups [Срок оценки: 18 months corrected age]
• Late gut microbiome comparison between study groups [Срок оценки: at 1 and 2 years corrected age.]
• Neurodevelopmental outcome as assessed by the Bayley Scales of Infant Development edition-IV (BSID-IV) [Срок оценки: 1 year and 2 years corrected age]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Washington — Seattle

Публикации

• 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

Идентификаторы

NCT: NCT05340465 · STUDY00015143 · R01HD107003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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