FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care

Introduction Even though respiratory support is a common intervention in paediatric critical care, there is no randomised controlled trial (RCT) evidence regarding the effectiveness of two commonly used modes of non-invasive respiratory support (NRS), continuous positive airway pressure (CPAP) and h...

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Main Authors: Mark J Peters, Padmanabhan Ramnarayan, Lyvonne N Tume, Kathryn M Rowan, David A Harrison, Alvin Richards-Belle, Peter Davis, Kevin P Morris, Zia Sadique, Laura Drikite, Richard Grieve, Julie Lester, Paul R Mouncey
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Language:English
Published: BMJ Publishing Group 2020-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/8/e038002.full
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author Mark J Peters
Padmanabhan Ramnarayan
Lyvonne N Tume
Kathryn M Rowan
David A Harrison
Alvin Richards-Belle
Peter Davis
Kevin P Morris
Zia Sadique
Laura Drikite
Richard Grieve
Julie Lester
Paul R Mouncey
author_facet Mark J Peters
Padmanabhan Ramnarayan
Lyvonne N Tume
Kathryn M Rowan
David A Harrison
Alvin Richards-Belle
Peter Davis
Kevin P Morris
Zia Sadique
Laura Drikite
Richard Grieve
Julie Lester
Paul R Mouncey
author_sort Mark J Peters
collection DOAJ
description Introduction Even though respiratory support is a common intervention in paediatric critical care, there is no randomised controlled trial (RCT) evidence regarding the effectiveness of two commonly used modes of non-invasive respiratory support (NRS), continuous positive airway pressure (CPAP) and high-flow nasal cannula therapy (HFNC). FIRST-line support for assistance in breathing in children is a master protocol of two pragmatic non-inferiority RCTs to evaluate the clinical and cost-effectiveness of HFNC (compared with CPAP) as the first-line mode of support in critically ill children.Methods and analysis We will recruit participants over a 30-month period at 25 UK paediatric critical care units (paediatric intensive care units/high-dependency units). Patients are eligible if admitted/accepted for admission, aged >36 weeks corrected gestational age and <16 years, and assessed by the treating clinician to require NRS for an acute illness (step-up RCT) or within 72 hours of extubation following a period of invasive ventilation (step-down RCT). Due to the emergency nature of the treatment, written informed consent will be deferred to after randomisation. Randomisation will occur 1:1 to CPAP or HFNC, stratified by site and age (<12 vs ≥12 months). The primary outcome is time to liberation from respiratory support for a continuous period of 48 hours. A total sample size of 600 patients in each RCT will provide 90% power with a type I error rate of 2.5% (one sided) to exclude the prespecified non-inferiority margin of HR of 0.75. Primary analyses will be undertaken separately in each RCT in both the intention-to-treat and per-protocol populations.Ethics and dissemination This master protocol received favourable ethical opinion from National Health Service East of England—Cambridge South Research Ethics Committee (reference: 19/EE/0185) and approval from the Health Research Authority (reference: 260536). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences.Trial registration number ISRCTN60048867
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spelling doaj-art-aad78ee5a36d4339a9848cd3cc17c8952025-08-20T02:18:16ZengBMJ Publishing GroupBMJ Open2044-60552020-08-0110810.1136/bmjopen-2020-038002FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical careMark J Peters0Padmanabhan Ramnarayan1Lyvonne N Tume2Kathryn M Rowan3David A Harrison4Alvin Richards-Belle5Peter Davis6Kevin P Morris7Zia Sadique8Laura Drikite9Richard Grieve10Julie Lester11Paul R Mouncey12Paediatric Intensive Care Unit, Great Ormond Street Hospital For Children NHS Trust, London, UK1 Children’s Acute Transport Service, Great Ormond Street Hospital For Children NHS Trust, London, UKSchool of Health and Society, University of Salford, Salford, UK1 Clinical Trials Unit, Intensive Care National Audit and Research Centre, London, UKIntensive Care National Audit and Research Centre, London, UK1 Intensive Care National Audit and Research Centre, London, UKPaediatric Intensive Care, Bristol Royal Hospital for Children, Bristol, UKPaediatric Intensive Care, Birmingham Children`s Hospital, Birmingham, West Midlands, UK5 Department of Health Services Research and Policy, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UKClinical Trials Unit, Intensive Care National Audit and Research Centre, London, UKDepartment of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK5 Parent representative, Sussex, UKIntensive Care National Audit and Research Centre, London, UKIntroduction Even though respiratory support is a common intervention in paediatric critical care, there is no randomised controlled trial (RCT) evidence regarding the effectiveness of two commonly used modes of non-invasive respiratory support (NRS), continuous positive airway pressure (CPAP) and high-flow nasal cannula therapy (HFNC). FIRST-line support for assistance in breathing in children is a master protocol of two pragmatic non-inferiority RCTs to evaluate the clinical and cost-effectiveness of HFNC (compared with CPAP) as the first-line mode of support in critically ill children.Methods and analysis We will recruit participants over a 30-month period at 25 UK paediatric critical care units (paediatric intensive care units/high-dependency units). Patients are eligible if admitted/accepted for admission, aged >36 weeks corrected gestational age and <16 years, and assessed by the treating clinician to require NRS for an acute illness (step-up RCT) or within 72 hours of extubation following a period of invasive ventilation (step-down RCT). Due to the emergency nature of the treatment, written informed consent will be deferred to after randomisation. Randomisation will occur 1:1 to CPAP or HFNC, stratified by site and age (<12 vs ≥12 months). The primary outcome is time to liberation from respiratory support for a continuous period of 48 hours. A total sample size of 600 patients in each RCT will provide 90% power with a type I error rate of 2.5% (one sided) to exclude the prespecified non-inferiority margin of HR of 0.75. Primary analyses will be undertaken separately in each RCT in both the intention-to-treat and per-protocol populations.Ethics and dissemination This master protocol received favourable ethical opinion from National Health Service East of England—Cambridge South Research Ethics Committee (reference: 19/EE/0185) and approval from the Health Research Authority (reference: 260536). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences.Trial registration number ISRCTN60048867https://bmjopen.bmj.com/content/10/8/e038002.full
spellingShingle Mark J Peters
Padmanabhan Ramnarayan
Lyvonne N Tume
Kathryn M Rowan
David A Harrison
Alvin Richards-Belle
Peter Davis
Kevin P Morris
Zia Sadique
Laura Drikite
Richard Grieve
Julie Lester
Paul R Mouncey
FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
BMJ Open
title FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
title_full FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
title_fullStr FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
title_full_unstemmed FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
title_short FIRST-line support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomised trials to evaluate the non-inferiority of high-flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care
title_sort first line support for assistance in breathing in children first abc a master protocol of two randomised trials to evaluate the non inferiority of high flow nasal cannula hfnc versus continuous positive airway pressure cpap for non invasive respiratory support in paediatric critical care
url https://bmjopen.bmj.com/content/10/8/e038002.full
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