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

NICHD Neonatal Research Network

Status and phase: Completed; Phase 3; Phase 2

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

Treatments: Drug: Erythropoietin; Other: Sham Comparator

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01203514

U10HD021415 (U.S. NIH Grant/Contract)

M01RR000997 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

U10HD034167 (U.S. NIH Grant/Contract)

M01RR002635 (U.S. NIH Grant/Contract)

M01RR006022 (U.S. NIH Grant/Contract)

U10HD027856 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD027881 (U.S. NIH Grant/Contract)

M01RR000750 (U.S. NIH Grant/Contract)

M01RR002172 (U.S. NIH Grant/Contract)

NICHD-NRN-0017

M01RR000039 (U.S. NIH Grant/Contract)

M01RR001032 (U.S. NIH Grant/Contract)

M01RR008084 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027871 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 318 patients

Sex: All

Ages: 24 hours to 96 days old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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318 participants in 4 patient groups

Trial 1 Experimental

Experimental group

Description:

Infants 401-1,000g birthweight

Treatment:

Drug: Erythropoietin

Trial 1: Sham Comparator

Sham Comparator group

Description:

Infants 401-1,000g birthweight

Treatment:

Other: Sham Comparator

Trial 2: Experimental

Experimental group

Description:

Infants 1,001-1,250g birth weight

Treatment:

Drug: Erythropoietin

Trial 2: Sham Comparator

Sham Comparator group

Description:

Infants 1,001-1,250g birth weight

Treatment:

Other: Sham Comparator