Evidence map›Paper›PMID 37906983›Full record

Trial reportDevelopmental neuroscience2024

Brain Injury Outcomes after Adjuvant Erythropoietin Neuroprotection for Moderate or Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Report from the HEAL Trial.

Jessica L Wisnowski, Sarah E Monsell, Stefan Bluml, Amy M Goodman, Yi Li, Bryan A Comstock, Patrick J Heagerty, Sandra E Juul, Yvonne W Wu, Robert C McKinstry and 2 more

Open access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Developmental neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
9.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Jessica L WisnowskiRadiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Sarah E MonsellBiostatistics, University of Washington, Seattle, Washington, USA.
Stefan BlumlRadiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Amy M GoodmanNeurology, University of California, San Francisco, California, USA.
Yi LiRadiology and Biomedical Imaging, University of California, San Francisco, California, USA.
Bryan A ComstockBiostatistics, University of Washington, Seattle, Washington, USA.
Patrick J HeagertyBiostatistics, University of Washington, Seattle, Washington, USA.
Sandra E JuulPediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
Yvonne W WuNeurology, University of California, San Francisco, California, USA.
Robert C McKinstryRadiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Amit M MathurPediatrics, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
HEAL Consortium
University of Washington · USUniversity of California, San Francisco · USWashington University in St. Louis · US

Funding

High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) CCCU01NS092764 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JUUL, SANDRA E, WU, YVONNE W · 2016 to 2020
$12.7M
High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) DCCU01NS092553 · NINDS · UNIVERSITY OF WASHINGTON · PI HEAGERTY, PATRICK J · 2016 to 2020
$1.7M
Validating MRS lipids as biomarkers of brain injury in neonates with hypoxic-ischemic encephalopathyK23HD099309 · NICHD · CHILDREN'S HOSPITAL OF LOS ANGELES · PI WISNOWSKI, JESSICA L · 2019 to 2023
$693k
NICHD NIH HHS K23 HD099309NINDS NIH HHS U01 NS092553NINDS NIH HHS U01 NS092764
6 · The paper itself

Abstract

introductionErythropoietin (Epo) is a putative neuroprotective therapy that did not improve overall outcomes in a phase 3 randomized controlled trial for neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). However, HIE is a heterogeneous disorder, and it remains to be determined whether Epo had beneficial effects on a subset of perinatal brain injuries.

methodsThis study was a secondary analysis of neuroimaging data from the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, which was conducted from 2016 to 2021 at 17 sites involving 23 US academic medical centers. Participants were neonates >36 weeks' gestation undergoing therapeutic hypothermia for moderate or severe HIE who received 5 doses of study drug (Epoetin alpha 1,000 U/kg/dose) or placebo in the first week of life. Treatment assignment was stratified by trial site and severity of encephalopathy. The primary outcome was the locus, pattern, and acuity of brain injury as determined by three independent readers using a validated HIE Magnetic Resonance Imaging (MRI) scoring system.

resultsOf the 500 infants enrolled in HEAL, 470 (94%) had high quality MRI data obtained at a median of 4.9 days of age (IQR: 4.5-5.8). The incidence of injury to the deep gray nuclei, cortex, white matter, brainstem and cerebellum was similar between Epo and placebo groups. Likewise, the distribution of injury patterns was similar between groups. Among infants imaged at less than 8 days (n = 414), 94 (23%) evidenced only acute, 93 (22%) only subacute and 89 (21%) both acute and subacute injuries, with similar distribution across treatment groups.

conclusionAdjuvant erythropoietin did not reduce the incidence of regional brain injury. Subacute brain injury was more common than previously reported, which has key implications for the development of adjuvant neuroprotective therapies for this population.

Indexed as

Hypoxia-Ischemia, BrainNeuroprotective AgentsBrain InjuriesEpoetin AlfaErythropoietinFemaleHumansHypothermia, InducedInfant, NewbornMagnetic Resonance ImagingMaleNeuroprotectionTreatment OutcomeEpoetin AlfaErythropoietinNeuroprotective AgentsErythropoietinLactateMRINeonatalNeuroprotection

Identifiers

PMID37906983
PMCPMC11249061
OpenAlexW4388038242

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.