Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO) : Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)
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ALBINO Study Group , Maiwald , C A , Annink , K V , Rüdiger , M , Benders , M J N L , Van Bel , F , Allegaert , K , Naulaers , G , Bassler , D , Klebermaß-Schrehof , K , Vento , M , Guimarães , H , Stiris , T , Cattarossi , L , Metsäranta , M , Vanhatalo , S , Mazela , J , Metsvaht , T & Jacobs , Y 2019 , ' Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO) : Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III) ' , BMC Pediatrics , vol. 19 , no. 1 , 210 . https://doi.org/10.1186/s12887-019-1566-8
| Title: | Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO) : Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III) |
| Author: | ALBINO Study Group; Maiwald, C.A.; Annink, K.V.; Rüdiger, M.; Benders, M.J.N.L.; Van Bel, F.; Allegaert, K.; Naulaers, G.; Bassler, D.; Klebermaß-Schrehof, K.; Vento, M.; Guimarães, H.; Stiris, T.; Cattarossi, L.; Metsäranta, M.; Vanhatalo, S.; Mazela, J.; Metsvaht, T.; Jacobs, Y. |
| Contributor organization: | HUS Children and Adolescents HUS Medical Imaging Center Children's Hospital Doctoral Programme in Clinical Research Department of Neurosciences Clinicum Doctoral Programme Brain & Mind Kliinisen neurofysiologian yksikkö |
| Date: | 2019 |
| Language: | eng |
| Number of pages: | 10 |
| Belongs to series: | BMC Pediatrics |
| ISSN: | 1471-2431 |
| DOI: | https://doi.org/10.1186/s12887-019-1566-8 |
| URI: | http://hdl.handle.net/10138/327644 |
| Abstract: | Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017. © 2019 The Author(s). |
| Subject: |
Allopurinol
Brain injury Cerebral palsy Childbirth outcome Hypothermia therapy Hypoxic-ischemic encephalopathy Neonatal oxygen deficiency Perinatal asphyxia allopurinol protein S100B antimetabolite Article birth weight controlled study disease severity double blind procedure drug effect drug efficacy drug safety drug screening echoencephalography electroencephalogram gestational age groups by age health care quality heart function human hypothermia hypoxic ischemic encephalopathy incidence major clinical study mental disease newborn newborn mortality nuclear magnetic resonance imaging perinatal asphyxia phase 3 clinical trial randomized controlled trial treatment outcome induced hypothermia infant mortality multicenter study (topic) multimodality cancer therapy phase 3 clinical trial (topic) procedures randomized controlled trial (topic) Antimetabolites Clinical Trials, Phase III as Topic Combined Modality Therapy Double-Blind Method Gestational Age Humans Hypothermia, Induced Hypoxia-Ischemia, Brain Infant Infant, Newborn Multicenter Studies as Topic Neurodevelopmental Disorders Randomized Controlled Trials as Topic 3123 Gynaecology and paediatrics |
| Peer reviewed: | Yes |
| Rights: | cc_by |
| Usage restriction: | openAccess |
| Self-archived version: | publishedVersion |
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