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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of Erythropoietin (EPO) on the Transfusion Requirements of Preterm Infants 401-1250 Grams: Two Multi-Center, Randomized, Double-Masked, Placebo Controlled Studies

Conditions
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Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature, Anemia, Neonatal

Intervention / Treatment
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* Drug: Erythropoietin
* Other: Sham Comparator


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 96 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trial 1 Experimental<br>Infants 401-1,000g birthweight | Drug: Erythropoietin<br>* Infants received 400 U/kg Erythropoietin (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.<br>* Other names: Human recombinant erythropoietin;|
| Sham Comparator: Trial 1: Sham Comparator<br>Infants 401-1,000g birthweight | Other: Sham Comparator<br>* Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.<br>|
| Experimental: Trial 2: Experimental<br>Infants 1,001-1,250g birth weight | Drug: Erythropoietin<br>* Infants received 400 U/kg Erythropoietin (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.<br>* Other names: Human recombinant erythropoietin;|
| Sham Comparator: Trial 2: Sham Comparator<br>Infants 1,001-1,250g birth weight | Other: Sham Comparator<br>* Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte transfusions in infants 401-1,000g birthweight |  | Hospital discharge or 35 weeks postmenstrual age | 
| Blood transfusions |  | Hospital discharge or 35 weeks postmenstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity, Erythrocyte transfusions, Erythropoietin (Epo), Blood loss, Phlebotomy