Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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.
Authors: Reema Garegrat, Atul Londhe, Swati Manerkar, Sudhindrashayana Fattepur, Laxmikant Deshmukh, Amol Joshi, Savitha Chandriah, Mallesh Kariyappa, Sahana Devadas, Theranirajan Ethirajan, Kalaivani Srivasan, Chinnathambi Kamalarathnam, Anitha Balachandran, Elango Krishnan, Deepthy Sahayaraj, Prathik Bandiya, Niranjan Shivanna, Constance Burgod, Ashwini Thayyil, Annie Alocious, Marianna Lanza, Pallavi Muraleedharan, Stuti Pant, Harini Venkateswaran, Maria Moreno Morales, Paolo Montaldo, Vaisakh Krishnan, Thaslima Kalathingal, Anagha Rajeev Joshi, Ajay Vare, G C Patil, Babu Peter Satyanathan, Pavan Hapat, Abhishek Deshmukh, Indramma Shivarudhrappa, Manjesh Kurupalya Annayappa, Mythili Baburaj, Christina Muradi, Esprance Fernandes, Nishad Thale, Ismat Jahan, Mohammed Shahidullah, Sadeka Moni Choudhury, Sanjoy Kumer Dey, Sutapa B Neogi, Rupsa Banerjee, Vanessa Rameh, Farah Alobeidi, Ellen Grant, Sandra E Juul, Martin Wilson, Enrico De Vita, Ronit Pressler, Paul Bassett, Seetha Shankaran, Sudhin Thayyil
Institutions: Imperial College London, Government Medical College, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Karnataka Institute of Medical Sciences, Bangalore Medical College and Research Institute, Madras Medical College, Indira Gandhi Institute of Child Health, University College London, Bangladesh Medical University, International Institute of Health Management Research, Delhi, Harvard University, Imperial College Healthcare NHS Trust, University of Washington, University of Birmingham, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, Seton Medical Center Austin, The University of Texas at Austin
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4396814741