Recombinant Human Erythropoietin Improve Neurodevelopmental Outcomes in Extremely Preterm Infants

NCT02745990 | Unknown DMC

• 1 other identifier: CZS-EPO
• Study Type: interventional
• Target: 440
• Locations: 0 countries
• Sites: N/A

Brief Summary

In the ELGAN (Extremely Low Gestational Age Newborn) study, abnormal brain structure and function were associated with intermittent or sustained systemic inflammation (ISSI). Since EPO has anti-inflammatory properties in the kidney and in muscle as well as growth/trophic properties. Based on its potential for neuroprotection, the prospective randomized and masked study was designed to determine whether rhEPO （500u/kg) was also effective in improving developmental outcomes for extremely low gestational age newborns.

Conditions

Developmental Disabilities

Keywords

erythropoietin; preterm; brain injury; cerebral palsy; PVL

Outcome Measures

Primary Outcomes (2)

• Mortality

  To compare the death rate of EPO and control groups at 2 years old

  2 years

• Incidence of neurological disability

  To assess the incidence of neurological disability of EPO and control groups at 2 years old

  2 years

Secondary Outcomes (7)

• Incidence of MDI<70

  2 years

• Incidence of cerebral palsy

  2 years

• Short-term complicatioins

  3 months

• Incidence of blindness

  2 years

• Incidence of deafness

  2 years

Study Arms (2)

EPO group

EXPERIMENTAL

In EPO group, The recombinant human erythropoietin (rhEPO) will be given by 500 U/kg/dose intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.

Drug: Recombinant human erythropoietin

Normal saline

PLACEBO COMPARATOR

Normal saline is administered the same volume with EPO, intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.

Drug: Normal saline

Interventions

Recombinant human erythropoietin DRUG

rhEPO is administered 500IU/kg, intravenously within 72h after birth, and every other day up to 32 weeks of corrected age.

Also known as: Epoietin Beta

EPO group

Normal saline DRUG

Normal salin is administered the same volume with rhEPO intravenously within 72h after birth, and every other day up to 32 weeks of corrected age..

Normal saline

Eligibility Criteria

• Age: 1 Day - 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants admitted to NICU wuth gestational age less than 28 weeks
• Age less than 3 days;
• parental informed consent.

You may not qualify if:

• Major life-threatening anomalies (brain, cardiac, chromosomal anomalies)
• Hematologic crises such as DIC, or hemolysis due to blood group incompatibilities
• Polycythemia (hematocrit \> 65);
• Hypertension
• Seizures
• Congenital infection

Sponsors & Collaborators

• Huiqing Sun: lead
• Zhengzhou University: collaborator
• Göteborg University: collaborator

Related Publications (11)

• Rees S, Harding R, Walker D. The biological basis of injury and neuroprotection in the fetal and neonatal brain. Int J Dev Neurosci. 2011 Oct;29(6):551-63. doi: 10.1016/j.ijdevneu.2011.04.004. Epub 2011 Apr 15.

  PMID: 21527338 RESULT

• Korzeniewski SJ, Allred E, Logan JW, Fichorova RN, Engelke S, Kuban KC, O'Shea TM, Paneth N, Holm M, Dammann O, Leviton A; ELGAN study investigators. Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates. PLoS One. 2015 Mar 20;10(3):e0115083. doi: 10.1371/journal.pone.0115083. eCollection 2015.

  PMID: 25793991 RESULT

• Moore EM, Bellomo R, Nichol AD. Erythropoietin as a novel brain and kidney protective agent. Anaesth Intensive Care. 2011 May;39(3):356-72. doi: 10.1177/0310057X1103900306.

  PMID: 21675055 RESULT

• Ohls RK, Kamath-Rayne BD, Christensen RD, Wiedmeier SE, Rosenberg A, Fuller J, Lacy CB, Roohi M, Lambert DK, Burnett JJ, Pruckler B, Peceny H, Cannon DC, Lowe JR. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics. 2014 Jun;133(6):1023-30. doi: 10.1542/peds.2013-4307. Epub 2014 May 12.

  PMID: 24819566 RESULT

• Zhu C, Kang W, Xu F, Cheng X, Zhang Z, Jia L, Ji L, Guo X, Xiong H, Simbruner G, Blomgren K, Wang X. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2009 Aug;124(2):e218-26. doi: 10.1542/peds.2008-3553. Epub 2009 Jul 27.

  PMID: 19651565 RESULT

• Brown MS, Eichorst D, Lala-Black B, Gonzalez R. Higher cumulative doses of erythropoietin and developmental outcomes in preterm infants. Pediatrics. 2009 Oct;124(4):e681-7. doi: 10.1542/peds.2008-2701. Epub 2009 Sep 28.

  PMID: 19786428 RESULT

• Leviton A, Kuban KC, Allred EN, Fichorova RN, O'Shea TM, Paneth N; ELGAN Study Investigators. Early postnatal blood concentrations of inflammation-related proteins and microcephaly two years later in infants born before the 28th post-menstrual week. Early Hum Dev. 2011 May;87(5):325-30. doi: 10.1016/j.earlhumdev.2011.01.043. Epub 2011 Feb 18.

  PMID: 21334149 RESULT

• O'Shea TM, Shah B, Allred EN, Fichorova RN, Kuban KCK, Dammann O, Leviton A; ELGAN Study Investigators. Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants. Brain Behav Immun. 2013 Mar;29:104-112. doi: 10.1016/j.bbi.2012.12.012. Epub 2013 Jan 4.

  PMID: 23295265 RESULT

• Lee SH, Li C, Lim SW, Ahn KO, Choi BS, Kim YS, Moon IS, Kim J, Bang BK, Yang CW. Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy. Am J Nephrol. 2005 Jan-Feb;25(1):64-76. doi: 10.1159/000084275. Epub 2005 Mar 2.

  PMID: 15746540 RESULT

• Contaldo C, Lindenblatt N, Elsherbiny A, Hogger DC, Borozadi MK, Vetter ST, Lang KS, Handschin AE, Giovanoli P. Erythropoietin requires endothelial nitric oxide synthase to counteract TNF-[alpha]-induced microcirculatory dysfunction in murine striated muscle. Shock. 2011 Mar;35(3):315-21. doi: 10.1097/SHK.0b013e3181fd0700.

  PMID: 20926979 RESULT

• Milne S, McDonald J, Comino EJ. The use of the Bayley Scales of Infant and Toddler Development III with clinical populations: a preliminary exploration. Phys Occup Ther Pediatr. 2012 Feb;32(1):24-33. doi: 10.3109/01942638.2011.592572. Epub 2011 Aug 4.

  PMID: 21812743 RESULT

MeSH Terms

Conditions

Developmental Disabilities; Premature Birth; Brain Injuries; Cerebral Palsy

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ligong Hou, BD

  Zhengzhou Children's Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of preterm infants intensive care unit

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: April 21, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share