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Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial

INTRODUCTION: Infants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-depe...

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Autores principales: Laing, Don, Walsh, Eamon, Alsweiler, Jane M, Hanning, Sara M, Meyer, Michael P, Ardern, Julena, Cutfield, Wayne S, Rogers, Jenny, Gamble, Greg D, Chase, J Geoffrey, Harding, Jane E, McKinlay, Christopher JD
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389093/
https://www.ncbi.nlm.nih.gov/pubmed/35977769
http://dx.doi.org/10.1136/bmjopen-2021-059452
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author Laing, Don
Walsh, Eamon
Alsweiler, Jane M
Hanning, Sara M
Meyer, Michael P
Ardern, Julena
Cutfield, Wayne S
Rogers, Jenny
Gamble, Greg D
Chase, J Geoffrey
Harding, Jane E
McKinlay, Christopher JD
author_facet Laing, Don
Walsh, Eamon
Alsweiler, Jane M
Hanning, Sara M
Meyer, Michael P
Ardern, Julena
Cutfield, Wayne S
Rogers, Jenny
Gamble, Greg D
Chase, J Geoffrey
Harding, Jane E
McKinlay, Christopher JD
author_sort Laing, Don
collection PubMed
description INTRODUCTION: Infants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-dependent manner to decrease insulin secretion. METHODS AND ANALYSIS: Phase IIB, double-blind, two-arm, parallel, randomised trial of diazoxide versus placebo in neonates ≥35 weeks’ gestation for treatment of severe (blood glucose concentration (BGC)<1.2 mmol/L or BGC 1.2 to <2.0 mmol/L despite two doses of buccal dextrose gel and feeding in a single episode) or recurrent (≥3 episodes <2.6 mmol/L in 48 hours) transitional hypoglycaemia. Infants are loaded with diazoxide 5 mg/kg orally and then commenced on a maintenance dose of 1.5 mg/kg every 12 hours, or an equal volume of placebo. The intervention is titrated from the third maintenance dose by protocol to target BGC in the range of 2.6–5.4 mmol/L. The primary outcome is time to resolution of hypoglycaemia, defined as the first point at which the following criteria are met concurrently for ≥24 hours: no intravenous fluids, enteral bolus feeding and normoglycaemia. Groups will be compared for the primary outcome using Cox’s proportional hazard regression analysis, expressed as adjusted HR with a 95% CI. ETHICS AND DISSEMINATION: This trial has been approved by the Health and Disability Ethics Committees of New Zealand (19CEN189). Findings will be disseminated in peer-reviewed journals, to clinicians and researchers at local and international conferences and to the public. TRIAL REGISTRATION NUMBER: ACTRN12620000129987.
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spelling pubmed-93890932022-09-06 Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial Laing, Don Walsh, Eamon Alsweiler, Jane M Hanning, Sara M Meyer, Michael P Ardern, Julena Cutfield, Wayne S Rogers, Jenny Gamble, Greg D Chase, J Geoffrey Harding, Jane E McKinlay, Christopher JD BMJ Open Paediatrics INTRODUCTION: Infants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-dependent manner to decrease insulin secretion. METHODS AND ANALYSIS: Phase IIB, double-blind, two-arm, parallel, randomised trial of diazoxide versus placebo in neonates ≥35 weeks’ gestation for treatment of severe (blood glucose concentration (BGC)<1.2 mmol/L or BGC 1.2 to <2.0 mmol/L despite two doses of buccal dextrose gel and feeding in a single episode) or recurrent (≥3 episodes <2.6 mmol/L in 48 hours) transitional hypoglycaemia. Infants are loaded with diazoxide 5 mg/kg orally and then commenced on a maintenance dose of 1.5 mg/kg every 12 hours, or an equal volume of placebo. The intervention is titrated from the third maintenance dose by protocol to target BGC in the range of 2.6–5.4 mmol/L. The primary outcome is time to resolution of hypoglycaemia, defined as the first point at which the following criteria are met concurrently for ≥24 hours: no intravenous fluids, enteral bolus feeding and normoglycaemia. Groups will be compared for the primary outcome using Cox’s proportional hazard regression analysis, expressed as adjusted HR with a 95% CI. ETHICS AND DISSEMINATION: This trial has been approved by the Health and Disability Ethics Committees of New Zealand (19CEN189). Findings will be disseminated in peer-reviewed journals, to clinicians and researchers at local and international conferences and to the public. TRIAL REGISTRATION NUMBER: ACTRN12620000129987. BMJ Publishing Group 2022-08-17 /pmc/articles/PMC9389093/ /pubmed/35977769 http://dx.doi.org/10.1136/bmjopen-2021-059452 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Paediatrics
Laing, Don
Walsh, Eamon
Alsweiler, Jane M
Hanning, Sara M
Meyer, Michael P
Ardern, Julena
Cutfield, Wayne S
Rogers, Jenny
Gamble, Greg D
Chase, J Geoffrey
Harding, Jane E
McKinlay, Christopher JD
Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title_full Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title_fullStr Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title_full_unstemmed Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title_short Oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: Neonatal Glucose Care Optimisation (NeoGluCO) study – a randomised controlled trial
title_sort oral diazoxide versus placebo for severe or recurrent neonatal hypoglycaemia: neonatal glucose care optimisation (neogluco) study – a randomised controlled trial
topic Paediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389093/
https://www.ncbi.nlm.nih.gov/pubmed/35977769
http://dx.doi.org/10.1136/bmjopen-2021-059452
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