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

• ClinicalTrials.gov Identifier: NCT01203514
• Recruitment Status: Completed
• First Posted: September 16, 2010
• Last Update Posted: September 26, 2017
• Sponsor: NICHD Neonatal Research Network
• Collaborator: National Center for Research Resources (NCRR)
• Information provided by: NICHD Neonatal Research Network

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Anemia, Neonatal	Drug: Erythropoietin; Other: Sham Comparator	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 318 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: August 1997
• Actual Primary Completion Date: August 1998
• Actual Study Completion Date: August 2000

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trial 1 Experimental; Infants 401-1,000g birthweight	Drug: Erythropoietin; 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.; Other Name: Human recombinant erythropoietin
Sham Comparator: Trial 1: Sham Comparator; Infants 401-1,000g birthweight	Other: Sham Comparator; Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.
Experimental: Trial 2: Experimental; Infants 1,001-1,250g birth weight	Drug: Erythropoietin; 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.; Other Name: Human recombinant erythropoietin
Sham Comparator: Trial 2: Sham Comparator; Infants 1,001-1,250g birth weight	Other: Sham Comparator; Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.

Outcome Measures

Primary Outcome Measures :

1. Erythrocyte transfusions in infants 401-1,000g birthweight [ Time Frame: Hospital discharge or 35 weeks postmenstrual age ]
2. Blood transfusions [ Time Frame: Hospital discharge or 35 weeks postmenstrual age ]

Eligibility Criteria

• Ages Eligible for Study: 24 Hours to 96 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06504

United States, District of Columbia

George Washington University

Washington, D.C., District of Columbia, United States, 20052

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30303

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

Harvard University

Cambridge, Massachusetts, United States, 02138

United States, Michigan

Wayne State University

Detroit, Michigan, United States, 48201

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87131

United States, Ohio

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States, 45267

United States, Tennessee

University of Tennessee

Memphis, Tennessee, United States, 38163

Sponsors and Collaborators

NICHD Neonatal Research Network

National Center for Research Resources (NCRR)

Investigators

• Study Director: Robin K. Ohls, MD; University of New Mexico
• Principal Investigator: Edward F. Donovan, MD; Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Barbara J. Stoll, MD; Emory University
• Principal Investigator: Ann R. Stark, MD; Brigham and Women's Hospital
• Principal Investigator: James A. Lemons, MD; Indiana University
• Principal Investigator: Sheldon B. Korones, MD; University of Tennessee
• Principal Investigator: Seetha Shankaran, MD; Wayne State University
• Study Director: Richard A. Ehrenkranz, MD; Yale University
• Principal Investigator: Raymond Bain, PhD; George Washington University

More Information

Additional Information:

NICHD Neonatal Research Network 

Publications of Results:

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.

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.

• Responsible Party: Robin K. Ohls, Lead Principal Investigator, University of New Mexico
• ClinicalTrials.gov Identifier: NCT01203514
• Other Study ID Numbers: NICHD-NRN-0017; U10HD027853 ( U.S. NIH Grant/Contract ); M01RR008084 ( U.S. NIH Grant/Contract ); U10HD027851 ( U.S. NIH Grant/Contract ); M01RR000039 ( U.S. NIH Grant/Contract ); U10HD034167 ( U.S. NIH Grant/Contract ); M01RR002635 ( U.S. NIH Grant/Contract ); M01RR002172 ( U.S. NIH Grant/Contract ); M01RR001032 ( U.S. NIH Grant/Contract ); U10HD027856 ( U.S. NIH Grant/Contract ); M01RR000750 ( U.S. NIH Grant/Contract ); U10HD027881 ( U.S. NIH Grant/Contract ); M01RR000997 ( U.S. NIH Grant/Contract ); U10HD021415 ( U.S. NIH Grant/Contract ); U10HD021385 ( U.S. NIH Grant/Contract ); U10HD027871 ( U.S. NIH Grant/Contract ); M01RR006022 ( U.S. NIH Grant/Contract )
• First Posted: September 16, 2010
• Last Update Posted: September 26, 2017
• Last Verified: September 2017

Keywords provided by NICHD Neonatal Research Network:

NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Prematurity; Erythrocyte transfusions; Erythropoietin (Epo); Blood loss; Phlebotomy

Additional relevant MeSH terms:

Anemia, Neonatal; Birth Weight; Body Weight; Anemia; Hematologic Diseases; Infant, Newborn, Diseases; Epoetin Alfa; Hematinics