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

Infant, Premature Clinical Trial

— EPO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01203514
• Other study ID #: NICHD-NRN-0017
• Secondary ID: U10HD027853M01RR
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 15, 2010
• Last updated: September 22, 2017
• Start date: August 1997
• Est. completion date: August 2000

Study information

• Verified date: September 2017
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: August 2000
• Est. primary completion date: August 1998
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 96 Days

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	Harvard University	Cambridge	Massachusetts
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Indiana University	Indianapolis	Indiana
United States	University of Tennessee	Memphis	Tennessee
United States	Yale University	New Haven	Connecticut
United States	George Washington University	Washington, D.C.	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erythrocyte transfusions in infants 401-1,000g birthweight		Hospital discharge or 35 weeks postmenstrual age
Primary	Blood transfusions		Hospital discharge or 35 weeks postmenstrual age

External Links

•   NICHD Neonatal Research Network