TY - JOUR
T1 - Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy
T2 - a multicentre double-blind pilot randomised controlled trial
AU - Garegrat, Reema
AU - Londhe, Atul
AU - Manerkar, Swati
AU - Fattepur, Sudhindrashayana
AU - Deshmukh, Laxmikant
AU - Joshi, Amol
AU - Chandriah, Savitha
AU - Kariyappa, Mallesh
AU - Devadas, Sahana
AU - Ethirajan, Theranirajan
AU - Srivasan, Kalaivani
AU - Kamalarathnam, Chinnathambi
AU - Balachandran, Anitha
AU - Krishnan, Elango
AU - Sahayaraj, Deepthy
AU - Bandiya, Prathik
AU - Shivanna, Niranjan
AU - Burgod, Constance
AU - Thayyil, Ashwini
AU - Alocious, Annie
AU - Lanza, Marianna
AU - Muraleedharan, Pallavi
AU - Pant, Stuti
AU - Venkateswaran, Harini
AU - Morales, Maria Moreno
AU - Montaldo, Paolo
AU - Krishnan, Vaisakh
AU - Kalathingal, Thaslima
AU - Joshi, Anagha Rajeev
AU - Vare, Ajay
AU - Patil, G C
AU - Satyanathan, Babu Peter
AU - Hapat, Pavan
AU - Deshmukh, Abhishek
AU - Shivarudhrappa, Indramma
AU - Annayappa, Manjesh Kurupalya
AU - Baburaj, Mythili
AU - Muradi, Christina
AU - Fernandes, Esprance
AU - Thale, Nishad
AU - Jahan, Ismat
AU - Shahidullah, Mohammed
AU - Choudhury, Sadeka Moni
AU - Dey, Sanjoy Kumer
AU - Neogi, Sutapa B
AU - Banerjee, Rupsa
AU - Rameh, Vanessa
AU - Alobeidi, Farah
AU - Grant, Ellen
AU - Juul, Sandra E
AU - Wilson, Martin
AU - Vita, Enrico De
AU - Pressler, Ronit
AU - Bassett, Paul
AU - Shankaran, Seetha
AU - Thayyil, Sudhin
PY - 2024/5/10
Y1 - 2024/5/10
N2 - Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195.
AB - Objective: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). Design: Double-blind pilot randomised controlled trial.Setting: Eight neonatal units in South Asia. Patients: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. Interventions: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. Main outcomes and measures: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. Results: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. Conclusions: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. Trial registration number: NCT05395195.
KW - Global Health
KW - Intensive Care Units, Neonatal
KW - Magnetic Resonance Imaging
KW - Neonatology
KW - Neurology
U2 - 10.1136/archdischild-2024-327107
DO - 10.1136/archdischild-2024-327107
M3 - Article
SN - 1359-2998
JO - Archives of disease in childhood. Fetal and neonatal edition
JF - Archives of disease in childhood. Fetal and neonatal edition
ER -