drugset / Trial / NCT02811263
High-dose Erythropoietin for Asphyxia and Encephalopathy
Phase 3
Completed
500 enrolled
University of California, San Francisco
Boston University · collabChildren's Hospital Los Angeles · collabChildren's Hospital Medical Center, Cincinnati · collabChildren's Hospital of Philadelphia · collabChildren's National Research Institute · collabCook Children's Medical Center · collabIndiana University · collabJohns Hopkins University · collabNationwide Children's Hospital · collabPediatrix · collabStanford University · collabUniversity of Chicago · collabUniversity of Minnesota · collabUniversity of New Mexico · collabUniversity of North Carolina · collabUniversity of Pittsburgh · collabUniversity of Texas · collabUniversity of Utah · collabUniversity of Washington · collabVanderbilt University · collabWashington University School of Medicine · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
Hypoxic-ischemic encephalopathy (HIE) occurs when a baby gets reduced blood flow and oxygen to the brain near the time of birth. This results in death or neurologic disabilities including cerebral palsy and cognitive impairment in up to half of affected infants. This clinical trial will determine if the drug erythropoietin (Epo) added to hypothermia (usual therapy) will improve outcomes for infants suffering from HIE.
Timeline
- Start
- 2017-01
- Primary completion
- 2021-10
- Completion
- 2022-04
Publications
- Background Juul SE, Comstock BA, Heagerty PJ, Mayock DE, Goodman AM, Hauge S, Gonzalez F, Wu YW. High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL): A Randomized Controlled Trial - Background, Aims, and Study Protocol. Neonatology. 2018;113(4):331-338. doi: 10.1159/000486820. Epub 2018 Mar 7.
- Background Wisnowski JL, Bluml S, Panigrahy A, Mathur AM, Berman J, Chen PK, Dix J, Flynn T, Fricke S, Friedman SD, Head HW, Ho CY, Kline-Fath B, Oveson M, Patterson R, Pruthi S, Rollins N, Ramos YM, Rampton J, Rusin J, Shaw DW, Smith M, Tkach J, Vasanawala S, Vossough A, Whitehead MT, Xu D, Yeom K, Comstock B, Heagerty PJ, Juul SE, Wu YW, McKinstry RC; HEAL Study Group. Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation. BMJ Open. 2021 Apr 22;11(4):e043852. doi: 10.1136/bmjopen-2020-043852.
- Results Chalak L, Redline RW, Goodman AM, Juul SE, Chang T, Yanowitz TD, Maitre N, Mayock DE, Lampland AL, Bendel-Stenzel E, Riley D, Mathur AM, Rao R, Van Meurs KP, Wu TW, Gonzalez FF, Flibotte J, Mietzsch U, Sokol GM, Ahmad KA, Baserga M, Weitkamp JH, Poindexter BB, Comstock BA, Wu YW. Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic-Ischemic Encephalopathy. J Pediatr. 2021 Oct;237:190-196. doi: 10.1016/j.jpeds.2021.06.023. Epub 2021 Jun 16.
- Results Wu YW, Comstock BA, Gonzalez FF, Mayock DE, Goodman AM, Maitre NL, Chang T, Van Meurs KP, Lampland AL, Bendel-Stenzel E, Mathur AM, Wu TW, Riley D, Mietzsch U, Chalak L, Flibotte J, Weitkamp JH, Ahmad KA, Yanowitz TD, Baserga M, Poindexter BB, Rogers EE, Lowe JR, Kuban KCK, O'Shea TM, Wisnowski JL, McKinstry RC, Bluml S, Bonifacio S, Benninger KL, Rao R, Smyser CD, Sokol GM, Merhar S, Schreiber MD, Glass HC, Heagerty PJ, Juul SE; HEAL Consortium. Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns. N Engl J Med. 2022 Jul 14;387(2):148-159. doi: 10.1056/NEJMoa2119660.
- Lew CO, Calabrese E, Chen JV, Tang F, Chaudhari G, Lee A, Faro J, Juul S, Mathur A, McKinstry RC, Wisnowski JL, Rauschecker A, Wu YW, Li Y. Artificial Intelligence Outcome Prediction in Neonates with Encephalopathy (AI-OPiNE). Radiol Artif Intell. 2024 Sep;6(5):e240076. doi: 10.1148/ryai.240076.
- Numis AL, Glass HC, Comstock BA, Gonzalez F, Maitre NL, Massey SL, Mayock DE, Mietzsch U, Natarajan N, Sokol GM, Bonifacio S, Van Meurs K, Thomas C, Ahmad K, Heagerty P, Juul SE, Wu YW, Wusthoff CJ. Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication. J Pediatr. 2024 May;268:113957. doi: 10.1016/j.jpeds.2024.113957. Epub 2024 Feb 13.
- Rao R, Comstock BA, Wu TW, Mietzsch U, Mayock DE, Gonzalez FF, Wood TR, Heagerty PJ, Juul SE, Wu YW. Time to Reaching Target Cooling Temperature and 2-year Outcomes in Infants with Hypoxic-Ischemic Encephalopathy. J Pediatr. 2024 Mar;266:113853. doi: 10.1016/j.jpeds.2023.113853. Epub 2023 Nov 23.
- Gonzalez FF, Voldal E, Comstock BA, Mayock DE, Goodman AM, Cornet MC, Wu TW, Redline RW, Heagerty P, Juul SE, Wu YW. Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy. Neonatology. 2023;120(6):760-767. doi: 10.1159/000533652. Epub 2023 Sep 22.
- Calabrese E, Wu Y, Scheffler AW, Wisnowski JL, McKinstry RC, Mathur A, Glass HC, Comstock BA, Heagerty PJ, Gillon S, Juul SE, Hess CP, Li Y. Correlating Quantitative MRI-based Apparent Diffusion Coefficient Metrics with 24-month Neurodevelopmental Outcomes in Neonates from the HEAL Trial. Radiology. 2023 Sep;308(3):e223262. doi: 10.1148/radiol.223262.
- Juul SE, Voldal E, Comstock BA, Massaro AN, Bammler TK, Mayock DE, Heagerty PJ, Wu YW, Numis AL; HEAL consortium. Association of High-Dose Erythropoietin With Circulating Biomarkers and Neurodevelopmental Outcomes Among Neonates With Hypoxic Ischemic Encephalopathy: A Secondary Analysis of the HEAL Randomized Clinical Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2322131. doi: 10.1001/jamanetworkopen.2023.22131.
- Juul SE, Comstock BA, Cornet MC, Gonzalez FF, Mayock DE, Glass HC, Schreiber MD, Heagerty PJ, Wu YW. Safety of High Dose Erythropoietin Used with Therapeutic Hypothermia as Treatment for Newborn Hypoxic-Ischemic Encephalopathy: Secondary Analysis of the HEAL Randomized Controlled Trial. J Pediatr. 2023 Jul;258:113400. doi: 10.1016/j.jpeds.2023.113400. Epub 2023 Apr 4.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | epoetin alfa | Protein / enzyme biologic | 1000 iu/kg | Intravenous |