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

NCT ID: NCT01203514

Last Updated: 2017-09-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

1997-08-31

Study Completion Date

2000-08-31

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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Trial 1 Experimental

Infants 401-1,000g birthweight

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

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.

Trial 1: Sham Comparator

Infants 401-1,000g birthweight

Group Type SHAM_COMPARATOR

Sham Comparator

Intervention Type OTHER

Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.

Trial 2: Experimental

Infants 1,001-1,250g birth weight

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

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.

Trial 2: Sham Comparator

Infants 1,001-1,250g birth weight

Group Type SHAM_COMPARATOR

Sham Comparator

Intervention Type OTHER

Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.

Interventions

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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.

Intervention Type DRUG

Sham Comparator

Infants in the placebo/control group received sham subcutaneous injections when intravenous access was not available.

Intervention Type OTHER

Other Intervention Names

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Human recombinant erythropoietin

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
Minimum Eligible Age

24 Hours

Maximum Eligible Age

96 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

NICHD Neonatal Research Network

NETWORK

Sponsor Role lead

Responsible Party

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University of New Mexico

Principal Investigators

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Robin K. Ohls, MD

Role: STUDY_DIRECTOR

University of New Mexico

Edward F. Donovan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Barbara J. Stoll, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Ann R. Stark, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

James A. Lemons, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Sheldon B. Korones, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tennessee

Seetha Shankaran, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Richard A. Ehrenkranz, MD

Role: STUDY_DIRECTOR

Yale University

Raymond Bain, PhD

Role: PRINCIPAL_INVESTIGATOR

George Washington University

Locations

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Yale University

New Haven, Connecticut, United States

Site Status

George Washington University

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

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Harvard University

Cambridge, Massachusetts, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

Cincinnati Children's Medical Center

Cincinnati, Ohio, United States

Site Status

University of Tennessee

Memphis, Tennessee, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 11581447 (View on PubMed)

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.

Reference Type RESULT
PMID: 15520109 (View on PubMed)

Related Links

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http://neonatal.rti.org/

NICHD Neonatal Research Network

Other Identifiers

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U10HD027853

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR008084

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000039

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034167

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR002635

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR002172

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR001032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027881

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR000997

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021415

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD021385

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M01RR006022

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NICHD-NRN-0017

Identifier Type: -

Identifier Source: org_study_id