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The Effects of Erythropoietin (EPO) on the Transfusion Requirements of Very Low Birth Weight Infants

Phase 2
Completed
Conditions
Anemia, Neonatal
Infant, Newborn
Infant, Premature
Infant, Low Birth Weight
Infant, Small for Gestational Age
Interventions
Other: Sham Comparator
Registration Number
NCT01203514
Lead Sponsor
NICHD Neonatal Research Network
Brief Summary

This study tested the safety and efficacy of transfusing erythropoietin (Epo) and iron in infants of \<1,250g birth weight. For infants 401-1,000g birth weight, we tested whether early erythropoietin (Epo) and iron therapy would decrease the number of transfusions received. For infants 1,001-1,250g birth weight, we tested whether early erythropoietin (Epo) and iron therapy would decrease the percentage of infants who received any transfusions.

Detailed Description

Critically ill preterm infants experience in the first 1-2 weeks after birth daily blood losses that may equal 5-10% of their total blood volume. Such losses and associated anemia typically result in multiple erythrocyte transfusions. This iatrogenic anemia commonly is followed by the anemia of prematurity, prompting additional transfusions.

This study tested the safety and efficacy of transfusing erythropoietin (Epo) and iron in infants of \<1,250g birth weight. For infants 401-1,000g birth weight (Trial 1), we tested whether early erythropoietin (Epo) and iron therapy would decrease the number of transfusions received. For infants 1,001-1,250g birth weight (Trial 2), we tested whether early erythropoietin (Epo) and iron therapy would decrease the percentage of infants who received any transfusions.

Therapy was initiated by day of life 4 and continued through the 35th postmenstrual week. Infants were randomized to receive either Epo and iron therapy or a sham procedure. Treated infants received 400 U/kg Epo 3 times weekly and a weekly intravenous infusion of 5 mg/kg iron dextran until they had an enteral intake of 60 mL/kg/d. Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available. Complete blood and reticulocyte counts were measured weekly, and ferritin concentrations were measured monthly.

Transfusions were administered according to protocol. Infants did not receive a transfusion solely to replace blood lost through phlebotomy. Infants who met transfusion criteria received a transfusion of 15 mL/kg packed red blood cells (PRBC) for a hematocrit of \>25% or 20 mL/kg PRBC for a hematocrit of \<=25%. Blood losses and transfusion data were recorded.

Trial 2 was terminated after enrollment of 118 infants after the Data and Safety Monitoring Committee reviewed the final results of Trial 1 and preliminary results of Trial 2. On the basis of these data, the Committee concluded that it was statistically unlikely that Trial 2 would demonstrate a significant decrease in the percentage of infants who would receive a transfusion during the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
318
Inclusion Criteria
  • Infants with a birth weight of 4010-1250g, <32 weeks' gestation, and 24-96 hours old at the time of study entry
  • Likely to survive >72 hours
  • Informed consent from a parent or guardian.
Exclusion Criteria
  • Major congenital anomaly
  • A positive direct antiglobulin test
  • Evidence of coagulopathy
  • Clinical seizures
  • Systolic blood pressure >100 mm Hg (in the absence of pressor support)
  • Absolute neutrophil count (ANC) of <=500/micro-L

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Trial 1: Sham ComparatorSham ComparatorInfants 401-1,000g birthweight
Trial 2: Sham ComparatorSham ComparatorInfants 1,001-1,250g birth weight
Trial 1 ExperimentalErythropoietinInfants 401-1,000g birthweight
Trial 2: ExperimentalErythropoietinInfants 1,001-1,250g birth weight
Primary Outcome Measures
NameTimeMethod
Erythrocyte transfusions in infants 401-1,000g birthweightHospital discharge or 35 weeks postmenstrual age
Blood transfusionsHospital discharge or 35 weeks postmenstrual age
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (9)

Emory University

🇺🇸

Atlanta, Georgia, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

Harvard University

🇺🇸

Cambridge, Massachusetts, United States

George Washington University

🇺🇸

Washington, D.C., District of Columbia, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

Cincinnati Children's Medical Center

🇺🇸

Cincinnati, Ohio, United States

University of Tennessee

🇺🇸

Memphis, Tennessee, United States

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