Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome

NCT03110341 | Unknown Phase 3 DMC

• 1 other identifier: XJTU1AF-CRF-2016-023
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Preterm and very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Magnetic resonance imaging (MRI) allows the characterization of specific features of encephalopathy of prematurity, including structural changes of brain white matter and gray matter. This study wants to investigate important evidence that early repeated high-dose rhEPO(5250 IU/kg) treatment improves long-term neurological outcomes in very preterm infants and without obvious adverse effects.

Conditions

Premature Infants; Intracranial Hemorrhages; Periventricular Leukomalacia; Cerebral Palsy

Outcome Measures

Primary Outcomes (1)

• Neurodevelopmental outcome

  To evaluate neurodevelopmental function via Bayley Scales of Infant Development, second edition (BSID-II) at 18 months corrected age and gain incidence of MDI\<70(Severe) or MDI\<85(Moderate).

  corrected age of 18 months

Secondary Outcomes (1)

• TBSS（Tract-based spatial statistics）

  corrected age of 40 weeks

Study Arms (2)

Erythropoietin

EXPERIMENTAL

Erythropoietin is administered 750U/kg intravenously every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections regardless of gestational age), starting with the first dose within 72 hours after birth. A single dose consisted of 750U EPO per kg of birth weight dissolved in 3mL/kg normal saline was administered intravenously during a period of 5 minutes.

Drug: Normal saline

Normal saline

PLACEBO COMPARATOR

Normal saline is administered 3ml/kg intravenously every other day for 2 weeks, starting with the first dose within 72 hours after birth. Similarly, the placebo dose consisted of 3mL of normal saline per kilogram birth weight was administered intravenously during a period of 5 minutes.

Drug: Erythropoietin

Interventions

Erythropoietin DRUG

rhEPO 750U/kg was injected within 72h after birth, subsequent injection was given every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections.

Also known as: Epoetin Beta

Normal saline

Normal saline DRUG

placebo (Normal saline 3 ml/kg birth weight) was injected within 72h after birth, subsequent injection was given every other day for 2 weeks.

Also known as: NaCl 0.9%

Erythropoietin

Eligibility Criteria

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

You may qualify if:

• premature infants who admitted to the neonatal intensive care unit(NICU) Within 72 hours after birth, gestational ages younger than 32 weeks, birth weight less than 1500 gram, informed consent was obtained from the infants' parents or guardians

You may not qualify if:

• born with anemia, polycythemia, hemolysis and other hematological diseases
• hypertension,
• convulsions,
• a genetically defined syndrome
• a severe congenital malformation adversely affecting life expectancy or neurodevelopment
• severe intraventricular hemorrhage
• thrombosis disease
• other fatal diseases or which can seriously affect the prognosis

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Xian Children's Hospital: collaborator
• Shaanxi Provincial People's Hospital: collaborator
• Second Affiliated Hospital of Xi'an Jiaotong University: collaborator
• Tang-Du Hospital: collaborator
• Xijing Hospital: collaborator
• Xi'an No.4 Hospital: collaborator
• Northwest Women's and Children's Hospital, Xi'an, Shaanxi: collaborator

Study Sites (1)

First Affiliated Hospital of Xian JiaotongUniversity

Xi'an, Shaanxi, 710061, China

RECRUITING

Related Publications (5)

• O'Gorman RL, Bucher HU, Held U, Koller BM, Huppi PS, Hagmann CF; Swiss EPO Neuroprotection Trial Group. Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants. Brain. 2015 Feb;138(Pt 2):388-97. doi: 10.1093/brain/awu363. Epub 2014 Dec 22.

  PMID: 25534356 RESULT

• Wu YW, Mathur AM, Chang T, McKinstry RC, Mulkey SB, Mayock DE, Van Meurs KP, Rogers EE, Gonzalez FF, Comstock BA, Juul SE, Msall ME, Bonifacio SL, Glass HC, Massaro AN, Dong L, Tan KW, Heagerty PJ, Ballard RA. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics. 2016 Jun;137(6):e20160191. doi: 10.1542/peds.2016-0191. Epub 2016 May 2.

  PMID: 27244862 RESULT

• Natalucci G, Latal B, Koller B, Ruegger C, Sick B, Held L, Bucher HU, Fauchere JC; Swiss EPO Neuroprotection Trial Group. Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years: A Randomized Clinical Trial. JAMA. 2016 May 17;315(19):2079-85. doi: 10.1001/jama.2016.5504.

  PMID: 27187300 RESULT

• Leuchter RH, Gui L, Poncet A, Hagmann C, Lodygensky GA, Martin E, Koller B, Darque A, Bucher HU, Huppi PS. Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 2014 Aug 27;312(8):817-24. doi: 10.1001/jama.2014.9645.

  PMID: 25157725 RESULT

• Song J, Sun H, Xu F, Kang W, Gao L, Guo J, Zhang Y, Xia L, Wang X, Zhu C. Recombinant human erythropoietin improves neurological outcomes in very preterm infants. Ann Neurol. 2016 Jul;80(1):24-34. doi: 10.1002/ana.24677. Epub 2016 May 11.

  PMID: 27130143 RESULT

MeSH Terms

Conditions

Premature Birth; Intracranial Hemorrhages; Leukomalacia, Periventricular; Cerebral Palsy

Interventions

Erythropoietin; epoetin beta; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Encephalomalacia; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Damage, Chronic

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Xihui Zhou, Doctor

  First Affiliated Hospital of Xian JiaotongUniversity

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xihui Zhou, Doctor

CONTACT

+8618991232230; zhouxih@xjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: April 12, 2017
• Study Start: April 10, 2017
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: October 2, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)