Multicentre, randomised trial to investigate early nasal high-flow therapy in paediatric acute hypoxaemic respiratory failure: a protocol for a randomised controlled trial-a Paediatric Acute respiratory Intervention Study (PARIS 2)

Donna Franklin; Deborah Shellshear; Franz E Babl; Luregn J Schlapbach; Ed Oakley; Meredith L Borland; Tobias Hoeppner; Shane George; Simon Craig; Jocelyn Neutze; Amanda Williams; Jason Acworth; Hamish McCay; Alex Wallace; Joerg Mattes; Vinay Gangathimn; Mark Wildman; John F Fraser; Susan Moloney; John Gavranich; John Waugh; Sue Hobbins; Rose Fahy; Simon Grew; Brenda Gannon; Kristen Gibbons; Stuart Dalziel; Andreas Schibler; PARIS and PREDICT

doi:10.1136/bmjopen-2019-030516

Multicentre, randomised trial to investigate early nasal high-flow therapy in paediatric acute hypoxaemic respiratory failure: a protocol for a randomised controlled trial-a Paediatric Acute respiratory Intervention Study (PARIS 2)

BMJ Open. 2019 Dec 18;9(12):e030516. doi: 10.1136/bmjopen-2019-030516.

Authors

Donna Franklin^{1

2

3

4}, Deborah Shellshear^{4

5

6}, Franz E Babl^{4

7

8

9}, Luregn J Schlapbach^{10

2

6}, Ed Oakley^{4

7

8

9}, Meredith L Borland^{4

11

12}, Tobias Hoeppner^{4

11}, Shane George^{10

2

4

13}, Simon Craig^{4

14

15}, Jocelyn Neutze^{4

16

17}, Amanda Williams^{4

7

8}, Jason Acworth^{2

4

5}, Hamish McCay¹⁸, Alex Wallace¹⁸, Joerg Mattes^{19

20}, Vinay Gangathimn^{4

21}, Mark Wildman^{4

21}, John F Fraser^{22

23}, Susan Moloney²⁴, John Gavranich²⁵, John Waugh²⁶, Sue Hobbins²⁷, Rose Fahy²⁷, Simon Grew²⁸, Brenda Gannon²⁹, Kristen Gibbons^{10

3}, Stuart Dalziel^{4

17

30

31}, Andreas Schibler^{10

2

3

4

6}; PARIS and PREDICT

Affiliations

¹ Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia d.franklin2@uq.edu.au.
² School of Medicine, The University Of Queensland, St Lucia, Queensland, Australia.
³ Mater Medical Research Institute, South Brisbane, Queensland, Australia.
⁴ Paediatric Research in Emergency Departments International Collaborative (PREDICT), Parkville, Victoria, Australia.
⁵ Emergency Department, Queensland Children's Hospital, South Brisbane, Queensland, Australia.
⁶ Queensland Children's Hospital, South Brisbane, Queensland, Australia.
⁷ Emergency Department, Royal Childrens Hospital, Parkville, Victoria, Australia.
⁸ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁹ Department of Paediatrics, Faculty of Medicine, Dentistry and Health Services, University of Melbourne, Melbourne, Victoria, Australia.
¹⁰ Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
¹¹ Emergency, Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia.
¹² University of Western Australia, School of Medicine, Divisions of Emergency Medicine and Paediatrics, Crawley, Western Australia, Australia.
¹³ Emergency Department, Gold Coast University Hospital, Southport, Queensland, Australia.
¹⁴ Emergency Department, Monash Medical Centre Clayton, Clayton, Victoria, Australia.
¹⁵ Department of Medicine, School of Clinical Science, Monash University, Clayton, Victoria, Australia.
¹⁶ KidzFirst Middlemore Emergency Department, Middlemore Hospital, Auckland, New Zealand.
¹⁷ University of Auckland, Auckland, New Zealand.
¹⁸ Paediatrics, Waikato Hospital, Hamilton, New Zealand.
¹⁹ Paediatrics, John Hunter Children's Hospital, Hunter Region Mail Centre, New South Wales, Australia.
²⁰ University of Newcastle, Priority Research Centre GrowUpWell, Callaghan, New South Wales, Australia.
²¹ Emergency Department, Townsville General Hospital, Townsville, Queensland, Australia.
²² Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, Queensland, Australia.
²³ Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Brisbane, Queensland, Australia.
²⁴ Paediatric Department, Gold Coast University Hospital, Southport, Queensland, Australia.
²⁵ Paediatrics, Ipswich Hospital, Ipswich, Queensland, Australia.
²⁶ Paediatrics, Caboolture Hospital, Caboolture, Queensland, Australia.
²⁷ Paediatrics, Prince Charles Hospital, Chermside, Queensland, Australia.
²⁸ Paediatrics, Redcliffe Hospital, Redcliffe, Queensland, Australia.
²⁹ The University of Queensland, Centre for Business and Economics of Health, St Lucia Qld, Queensland, Australia.
³⁰ Starship Children's Health, Emergency Department, Newmarket, New Zealand.
³¹ Department of Surgery and Paediatrics, Child and Youth Health, University of Auckland, Auckland, New Zealand.

Abstract

Introduction: Acute hypoxaemic respiratory failure (AHRF) in children is the most frequent reason for non-elective hospital admission. During the initial phase, AHRF is a clinical syndrome defined for the purpose of this study by an oxygen requirement and caused by pneumonia, lower respiratory tract infections, asthma or bronchiolitis. Up to 20% of these children with AHRF can rapidly deteriorate requiring non-invasive or invasive ventilation. Nasal high-flow (NHF) therapy has been used by clinicians for oxygen therapy outside intensive care settings to prevent escalation of care. A recent randomised trial in infants with bronchiolitis has shown that NHF therapy reduces the need to escalate therapy. No similar data is available in the older children presenting with AHRF. In this study we aim to investigate in children aged 1 to 4 years presenting with AHRF if early NHF therapy compared with standard-oxygen therapy reduces hospital length of stay and if this is cost-effective compared with standard treatment.

Methods and analysis: The study design is an open-labelled randomised multicentre trial comparing early NHF and standard-oxygen therapy and will be stratified by sites and into obstructive and non-obstructive groups. Children aged 1 to 4 years (n=1512) presenting with AHRF to one of the participating emergency departments will be randomly allocated to NHF or standard-oxygen therapy once the eligibility criteria have been met (oxygen requirement with transcutaneous saturation <92%/90% (dependant on hospital standard threshold), diagnosis of AHRF, admission to hospital and tachypnoea ≥35 breaths/min). Children in the standard-oxygen group can receive rescue NHF therapy if escalation is required. The primary outcome is hospital length of stay. Secondary outcomes will include length of oxygen therapy, proportion of intensive care admissions, healthcare resource utilisation and associated costs. Analyses will be conducted on an intention-to-treat basis.

Ethics and dissemination: Ethics approval has been obtained in Australia (HREC/15/QRCH/159) and New Zealand (HDEC 17/NTA/135). The trial commenced recruitment in December 2017. The study findings will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. Authorship of all publications will be decided by mutual consensus of the research team.

Trial registration number: ACTRN12618000210279.

Keywords: children; oxygen therapy; paediatric; respiratory disease; respiratory support.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
Early Medical Intervention
Humans
Infant
Multicenter Studies as Topic / methods*
Nose
Oxygen Inhalation Therapy / methods*
Randomized Controlled Trials as Topic / methods*
Respiratory Insufficiency / therapy*

Associated data

ANZCTR/ACTRN12618000210279