Journal Article

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial

Satyanathan, Babu Peter, Londhe, Atul, Kamalarathnam, Chinnathambi, Muradi, Christina, Bassett, Paul, Fattepur, Sudhindrashayana, Joshi, Anagha Rajeev, Patil, G C, Muraleedharan, Pallavi, Bandiya, Prathik, Sahayaraj, Deepthy, Fernandes, Esprance, Thayyil, Ashwini, Dey, Sanjoy Kumer, Joshi, Amol, Burgod, Constance, Annayappa, Manjesh Kurupalya, Kalathingal, Thaslima, Thayyil, Sudhin, Jahan, Ismat, Hapat, Pavan, Pant, Stuti, Lanza, Marianna, Srivasan, Kalaivani, Alobeidi, Farah, Chandriah, Savitha, Baburaj, Mythili, Vita, Enrico De, Venkateswaran, Harini, Garegrat, Reema, Neogi, Sutapa B, Shivanna, Niranjan, Shivarudhrappa, Indramma, Wilson, Martin, Devadas, Sahana, Thale, Nishad, Ethirajan, Theranirajan, Shahidullah, Mohammed, Vare, Ajay, Rameh, Vanessa, Pressler, Ronit, Banerjee, Rupsa, Juul, Sandra E, Deshmukh, Laxmikant, Krishnan, Vaisakh, Grant, Ellen, Shankaran, Seetha, Kariyappa, Mallesh, Deshmukh, Abhishek, Manerkar, Swati, Balachandran, Anitha, Alocious, Annie, Montaldo, Paolo, Choudhury, Sadeka Moni, Morales, Maria Moreno, Krishnan, Elango

2024

Overview

ObjectiveTo examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).DesignDouble-blind pilot randomised controlled trial.SettingEight neonatal units in South Asia.PatientsNeonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023.InterventionsErythropoietin (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 measuresFeasibility of randomisation, drug administration and assessment of brain injury using MRI.ResultsOf 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.ConclusionsBrain 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.

• Publisher: BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Birth weight / Brain research / Clinical trials / Consent / Double-Blind Method / Drug dosages / Erythropoietin - therapeutic use / Feasibility Studies / Female / Global Health / Humans / Hypothermia / Hypoxia / Hypoxia-Ischemia, Brain - drug therapy / Infant, Newborn / Intensive care / Intensive Care Units, Neonatal / Ischemia / Magnetic Resonance Imaging / Male / Mortality / Neonates / Neonatology / Neurology / Newborn babies / Original Research / Pilot Projects / Pulmonary hypertension / Thromboembolism / Thrombosis / Traumatic brain injury / Treatment Outcome