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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01203514
First received: September 15, 2010
Last updated: January 9, 2011
Last verified: September 2010
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Erythrocyte transfusions in infants 401-1,000g birthweight [ Time Frame: Hospital discharge or 35 weeks postmenstrual age ] [ Designated as safety issue: Yes ]
  • Blood transfusions [ Time Frame: Hospital discharge or 35 weeks postmenstrual age ] [ Designated as safety issue: Yes ]

Enrollment: 318
Study Start Date: August 1997
Study Completion Date: August 2000
Primary Completion Date: August 1998 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   up to 96 Days
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01203514

Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06504
United States, District of Columbia
George Washington University
Washington, 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
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:
Publications:
Responsible Party: Robin K. Ohls, Lead Principal Investigator, University of New Mexico
ClinicalTrials.gov Identifier: NCT01203514     History of Changes
Other Study ID Numbers: NICHD-NRN-0017, U10HD027853, M01RR008084, U10HD027851, M01RR000039, U10HD034167, M01RR002635, M01RR002172, M01RR001032, U10HD027856, M01RR000750, U10HD027881, M01RR000997, U10HD021415, U10HD021385, U10HD027871, M01RR006022
Study First Received: September 15, 2010
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
NICHD Neonatal Research Network
Extremely Low Birth Weight (ELBW)
Prematurity
Erythrocyte transfusions
Erythropoietin (Epo)
Blood loss
Phlebotomy

Additional relevant MeSH terms:
Anemia
Anemia, Neonatal
Birth Weight
Hematologic Diseases
Infant, Newborn, Diseases
Body Weight
Signs and Symptoms
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014