Trial of Darbepoetin Plus Slow-release Intravenous Iron to Decrease Transfusions and Improve Iron Status and Neurodevelopment in Preterm Infants
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL
研究概览
简要总结
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
详细描述
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). 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Group 1 will be unblinded. In Groups 2-5 all infants will receive Darbe, and the iron preparation and dose will be blinded.
入排标准
- 年龄范围
- — 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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
干预措施: Darbepoetin Alfa (Drug)
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
干预措施: Darbepoetin Alfa (Drug)
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
干预措施: Darbepoetin Alfa (Drug)
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
干预措施: Darbepoetin Alfa (Drug)
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.
干预措施: Oral iron supplements (Drug)
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
干预措施: Low Molecular Weight Iron Dextran (Drug)
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
干预措施: Low Molecular Weight Iron Dextran (Drug)
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
干预措施: Ferumoxytol injection (Drug)
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
干预措施: Ferumoxytol injection (Drug)
结局指标
主要结局
Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL
时间窗: 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
Volume of blood transfusions
时间窗: 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
Plasma Ferritin at 35-36 weeks PMA
时间窗: 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
Number of Blood transfusions
时间窗: 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.
次要结局
- Rate of referral for Brainstem auditory evoked response(at hospital discharge, near 36 weeks postmenstrual age)
- Late gut microbiome comparison between study groups(at 1 and 2 years corrected age.)
- Hematocrit(Birth to 36 weeks PMA)
- Neurodevelopmental outcome as assessed by the Bayley Scales of Infant Development edition-IV (BSID-IV)(1 year and 2 years corrected age)
- 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))
- Early gut microbiome comparison between study groups(at 7 days (prior to iron supplementation) and 4 weeks after birth)
- Rate of pass/fail the General Movements Assessments (GMA)(3 months corrected age)
- Safety of IV iron(Birth to 36 weeks postmenstrual age (or prior to discharge if this occurs prior to 36 weeks))
- Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups(18 months corrected age)
- Scores for the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be compared between groups(6 months corrected age)
研究者
Kendell German
Associate Professor: School of Medicine, Pediatrics
University of Washington