A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
16 01 2020
16 01 2020
Historique:
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
11
2
2020
Statut:
ppublish
Résumé
High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).
Sections du résumé
BACKGROUND
High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.
METHODS
In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.
RESULTS
A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.
CONCLUSIONS
High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).
Identifiants
pubmed: 31940698
doi: 10.1056/NEJMoa1907423
pmc: PMC7060076
mid: NIHMS1565143
doi:
Substances chimiques
Erythropoietin
11096-26-7
Banques de données
ClinicalTrials.gov
['NCT01378273']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
233-243Subventions
Organisme : NICHD NIH HHS
ID : P50 HD103524
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS077955
Pays : United States
Organisme : NINDS NIH HHS
ID : U01NS077953-01
Pays : United States
Organisme : NINDS NIH HHS
ID : U01NS077955
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS077953
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS096115
Pays : United States
Investigateurs
Billy Thomas
(B)
Nahed Elhassan
(N)
Sarah Mulkey
(S)
Philip Dydynski
(P)
Vivek K Vijayamadhavan
(VK)
Neil Mulrooney
(N)
Bradley Yoder
(B)
Jordan S Kase
(JS)
Jennifer Check
(J)
Semsa Gogcu
(S)
Erin Osterholm
(E)
Sara Ramel
(S)
Catherine Bendel
(C)
Cheryl Gale
(C)
Thomas George
(T)
Michael Georgieff
(M)
Tate Gisslen
(T)
Sixto Guiang
(S)
Anne Hall
(A)
Dana Johnson
(D)
Katie Pfister
(K)
Heather Podgorski
(H)
Kari Roberts
(K)
Erin Stepka
(E)
Melissa Engel
(M)
Heidi Kamrath
(H)
Johannah Scheurer
(J)
Angela Hanson
(A)
Katherine Satrom
(K)
Susan Pfister
(S)
Ann Simones
(A)
Erin Plummer
(E)
Elizabeth Zorn
(E)
Camilia R Martin
(CR)
Deirdre O'Reilly
(D)
Nicolas Porta
(N)
Catalina Bazacliu
(C)
Jonathan Williams
(J)
Dhanashree Rajderkar
(D)
Frances Northington
(F)
Raul Chavez Valdez
(R)
Sandra Beauman
(S)
Patel Saurabhkumar
(P)
Magaly Diaz-Barbosa
(M)
Arturo Serize
(A)
Jorge Jordan
(J)
Debbie Ott
(D)
Ariana Franco Mora
(A)
Pamela Hedrick
(P)
Vicki Flynn
(V)
Amy Silvia
(A)
Bailey Clopp
(B)
John B Feltner
(JB)
Isabella Esposito
(I)
Stephanie Hauge
(S)
Samantha Nikirk
(S)
Andrea Purnell
(A)
Emilie Loy
(E)
Natalie Sikes
(N)
Melanie Mason
(M)
Jana McConnell
(J)
Tiffany Brown
(T)
Henry Harrison
(H)
Denise Pearson
(D)
Tammy Drake
(T)
Jocelyn Wright
(J)
Debra Walden
(D)
Annette Guy
(A)
Jennifer Nason
(J)
Morgan Talbot
(M)
Kristen Lee
(K)
Sarah Penny
(S)
Terri Boles
(T)
Melanie Drummond
(M)
Katy Kohlleppel
(K)
Charmaine Kathen
(C)
Brian Kaletka
(B)
Shania Gonzales
(S)
Cathy Worwa
(C)
Molly Fishe
(M)
Tyler Richter
(T)
Alexander Ginder
(A)
Brixen Reich
(B)
Carrie Rau
(C)
Manndi Loertscher
(M)
Laura Bledsoe
(L)
Kandace McGrath
(K)
Kimberlee Weaver Lewis
(K)
Jill Burnett
(J)
Susan Schaefer
(S)
Karie Bird
(K)
Clare Giblin
(C)
Rita Daly
(R)
Kristi Lanier
(K)
Kelly Warden
(K)
Jenna Wassenaar
(J)
Jensina Ericksen
(J)
Bridget Davern
(B)
Mary Pat Osborne
(MP)
Brittany Gregorich
(B)
Neha Talele
(N)
Evelyn Obregon
(E)
Tiglath Ziyeh
(T)
Molly Clarke
(M)
Rachel E Wegner
(RE)
Palak Patel
(P)
Molly Schau
(M)
Annamarie Russow
(A)
Kelly Curry
(K)
Susan Sinnamon
(S)
Lisa Barnhart
(L)
Charlamaine Parkinson
(C)
Mary Hanson
(M)
Elizabeth Kuan
(E)
Conra Backstrom Lacy
(C)
Edshelee M Galvis
(EM)
Susana Bombino
(S)
Denise Martinez
(D)
Suzi Bell
(S)
Corrie Long
(C)
Cathy Longa
(C)
Michael Westerveld
(M)
Stacy McConkey
(S)
Anne Hay
(A)
Niranjana Natarajan
(N)
Shari Gaudette
(S)
Sarah Cobb
(S)
Gregory Sharp
(G)
Elizabeth Schumacher
(E)
Leslie Schuschke
(L)
Charlotte Frey
(C)
Mario Fierro
(M)
Lois Gilmore
(L)
Pamela Lundequam
(P)
Ronald Hoekstra
(R)
Anastasia Ketko
(A)
Nina Perdue
(N)
Sean Cunningham
(S)
Kelly Stout
(K)
Becky Hall
(B)
Galina Morshedzadeh
(G)
Betsy Ostrander
(B)
Sarah Winter
(S)
Lauren Cox
(L)
Matthew A Rainaldi
(MA)
Sarah Hensley
(S)
Melissa Morris
(M)
Dia Roberts
(D)
Melissa Tuttle
(M)
Christopher Boys
(C)
Solveig Hultgren
(S)
Elizabeth I Pierpont
(EI)
Nancy Fahim
(N)
Tom George
(T)
Kelly E King
(KE)
Katherine Bataglia
(K)
Cathy Neis
(C)
Mark Bergeron
(M)
Cristina Miller
(C)
Cara Accomando
(C)
Jennifer Anne Gavin
(JA)
Elizabeth Maczek
(E)
Susan Marakovitz
(S)
Aimee Knorr
(A)
Vincent C Smith
(VC)
Jane E Stewart
(JE)
Marie Weissbourd
(M)
Raye-Ann deRegnier
(RA)
Nana Matoba
(N)
Shelly C Heaton
(SC)
Erika M Cascio
(EM)
Janet Brady
(J)
Suman Ghosh
(S)
Jessica Ditto
(J)
Mary Leppert
(M)
Jean Lowe
(J)
Janell Fuller
(J)
Tara DuPont
(T)
Robin Ohls
(R)
Pamela Kloska
(P)
Saurabh Patel
(S)
Lauren Carbonell
(L)
Anna Maria Patino-Fernandez
(AM)
Carmen de Lerma
(C)
Kelly McDonough
(K)
Maiana De Cortada
(M)
Lacy Chavis
(L)
Jane Shannon
(J)
Bryan A Comstock
(BA)
Patrick J Heagerty
(PJ)
Mark A Konodi
(MA)
Christopher Nefcy
(C)
Phuong T Vu
(PT)
Karl C K Kuban
(KCK)
Jean R Lowe
(JR)
T Michael O'Shea
(TM)
Manjiri Dighe
(M)
Todd Richards
(T)
Dennis W W Shaw
(DWW)
Colin Studholme
(C)
Christopher M Traudt
(CM)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
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