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
{"title":"Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.","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","doi":"10.1136/archdischild-2024-327107","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).</p><p><strong>Design: </strong>Double-blind pilot randomised controlled trial.</p><p><strong>Setting: </strong>Eight neonatal units in South Asia.</p><p><strong>Patients: </strong>Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023.</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcomes and measures: </strong>Feasibility of randomisation, drug administration and assessment of brain injury using MRI.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration number: </strong>NCT05395195.</p>","PeriodicalId":8177,"journal":{"name":"Archives of Disease in Childhood - Fetal and Neonatal Edition","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503063/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Disease in Childhood - Fetal and Neonatal Edition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/archdischild-2024-327107","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Archives of Disease in Childhood is an international peer review journal that aims to keep paediatricians and others up to date with advances in the diagnosis and treatment of childhood diseases as well as advocacy issues such as child protection. It focuses on all aspects of child health and disease from the perinatal period (in the Fetal and Neonatal edition) through to adolescence. ADC includes original research reports, commentaries, reviews of clinical and policy issues, and evidence reports. Areas covered include: community child health, public health, epidemiology, acute paediatrics, advocacy, and ethics.