Clinical trial NCT01203514: The Effects of Erythropoietin (EPO) on the Transfusion Requirements of Very Low Birth Weight Infants
Official title: The Effects of Erythropoietin (EPO) on the Transfusion Requirements of Preterm Infants 401-1250 Grams: Two Multi-Center, Randomized, Double-Masked, Placebo Controlled Studies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Infant, Newborn
Infant, Low Birth Weight
Infant, Small for Gestational Age
Infant, Premature
Anemia, Neonatal
Keywords: NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Erythrocyte transfusions
Erythropoietin (Epo)
Blood loss
Phlebotomy
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2010-09-16
Enrollment: 318
Sex: ALL
Minimum age (years): 24
Maximum age (years): 96
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Erythrocyte transfusions in infants 401-1,000g birthweight
timeFrame: Hospital discharge or 35 weeks postmenstrual age
measure: Blood transfusions
timeFrame: Hospital discharge or 35 weeks postmenstrual age
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington, D.C.
country: United States
facility: George Washington University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Cambridge
country: United States
facility: Harvard University
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
Study officials:
affiliation: University of New Mexico
name: Robin K. Ohls, MD
role: STUDY_DIRECTOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Edward F. Donovan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara J. Stoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Ann R. Stark, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: James A. Lemons, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Tennessee
name: Sheldon B. Korones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: STUDY_DIRECTOR
affiliation: George Washington University
name: Raymond Bain, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ohls RK, Ehrenkranz RA, Wright LL, Lemons JA, Korones SB, Stoll BJ, Stark AR, Shankaran S, Donovan EF, Close NC, Das A. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics. 2001 Oct;108(4):934-42. doi: 10.1542/peds.108.4.934.
citation: Ohls RK, Ehrenkranz RA, Das A, Dusick AM, Yolton K, Romano E, Delaney-Black V, Papile LA, Simon NP, Steichen JJ, Lee KG; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron. Pediatrics. 2004 Nov;114(5):1287-91. doi: 10.1542/peds.2003-1129-L.