Clinical trial NCT05340465: Darbe Plus IV Iron to Decrease Transfusions While Maintaining Iron Sufficiency in Preterm Infants
Official title: Trial of Darbepoetin Plus Slow-release Intravenous Iron to Decrease Transfusions and Improve Iron Status and Neurodevelopment in Preterm Infants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prematurity
Iron-deficiency
Iron Deficiency Anemia
Iron Malabsorption
Keywords: prematurity
iron deficiency
anemia
darbepoetin
IV Iron
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-04-22
Enrollment: 120
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * 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 purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma Ferritin at 35-36 weeks PMA
timeFrame: birth to 36 weeks postmenstrual age
measure: Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL
timeFrame: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)
measure: Number of Blood transfusions
timeFrame: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)
measure: Volume of blood transfusions
timeFrame: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)
Secondary outcomes:
measure: Number and percent of patients per group that remain transfusion free
timeFrame: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)
measure: Hematocrit
timeFrame: Birth to 36 weeks PMA
measure: Safety of IV iron
timeFrame: Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks)
measure: Early gut microbiome comparison between study groups
timeFrame: at 7 days (prior to iron supplementation) and 4 weeks after birth
measure: Rate of referral for Brainstem auditory evoked response
timeFrame: at hospital discharge, near 36 weeks postmenstrual age
measure: Rate of pass/fail the General Movements Assessments (GMA)
timeFrame: 3 months corrected age
measure: Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups
timeFrame: 6 months corrected age
measure: Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups
timeFrame: 18 months corrected age
measure: Late gut microbiome comparison between study groups
timeFrame: at 1 and 2 years corrected age.
measure: Neurodevelopmental outcome as assessed by the Bayley Scales of Infant Development edition-IV (BSID-IV)
timeFrame: 1 year and 2 years corrected age
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Sandra E Juul, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: