BACKGROUND: Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity. METHODS: We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 microg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489. FINDINGS:Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34 x 10(9)/L/day; 95% CI 0.12-0.56). There was no significant difference in sepsis-free survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% CI -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit. INTERPRETATION: Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.
RCT Entities:
BACKGROUND: Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity. METHODS: We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 microg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489. FINDINGS: Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34 x 10(9)/L/day; 95% CI 0.12-0.56). There was no significant difference in sepsis-free survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% CI -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit. INTERPRETATION: Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.
Authors: Kathrin Steinwede; Ole Tempelhof; Kristine Bolte; Regina Maus; Jennifer Bohling; Bianca Ueberberg; Florian Länger; John W Christman; James C Paton; Kjetil Ask; Shyam Maharaj; Martin Kolb; Jack Gauldie; Tobias Welte; Ulrich A Maus Journal: J Immunol Date: 2011-10-14 Impact factor: 5.422
Authors: Rían Hayes; Jack Hartnett; Gergana Semova; Cian Murray; Katherine Murphy; Leah Carroll; Helena Plapp; Louise Hession; Jonathan O'Toole; Danielle McCollum; Edna Roche; Elinor Jenkins; David Mockler; Tim Hurley; Matthew McGovern; John Allen; Judith Meehan; Frans B Plötz; Tobias Strunk; Willem P de Boode; Richard Polin; James L Wynn; Marina Degtyareva; Helmut Küster; Jan Janota; Eric Giannoni; Luregn J Schlapbach; Fleur M Keij; Irwin K M Reiss; Joseph Bliss; Joyce M Koenig; Mark A Turner; Christopher Gale; Eleanor J Molloy Journal: Pediatr Res Date: 2021-11-06 Impact factor: 3.756
Authors: Deena Gibbons; Paul Fleming; Alex Virasami; Marie-Laure Michel; Neil J Sebire; Kate Costeloe; Robert Carr; Nigel Klein; Adrian Hayday Journal: Nat Med Date: 2014-09-21 Impact factor: 53.440