Why are we conducting the PARIS II study?
For children who present to the emergency department with respiratory illnesses such as pneumonia, asthma, bronchitis or any form of common respiratory illness this can be a stressful time for the child and family. A new therapy, which has emerged in the last ten years and has become common practice in many hospitals which needs greater evidence to support its use in children with respiratory illnesses. This study will provide answers to which children improve quicker and require less time in hospital. The results of this study will impact on how we care for children with common respiratory illnesses worldwide.
What is the aim of the PARIS II study?
This study aims to develop a multi-centre trial and to assess which children with common respiratory illnesses such as pneumonia, bronchitis and asthma to name a few benefit using High Flow therapy. For this purpose we will perform a study comparing current best practice (standard oxygen delivery via subnasal cannula or facemask) versus High Flow therapy. With the introduction of this simple to use respiratory system in regional and tertiary centres we aim to investigate if High Flow therapy is the superior treatment for these children in comparison to standard oxygen delivery, and to investigate if there is a reduced length of hospital stay.
What is high flow therapy?
High Flow therapy is a type of respiratory support that delivers a higher flow of medical gas to a patient through an interface (nasal cannula) intended to achieve the following for children with respiratory distress:
- Provide oxygen (if required)
- Provide positive expiratory pressure which allows the tiny sacs in the lungs called alveoli to open up and improve gas exchange
- Create a wash-out of the upper airway dead space to improve the benefit of flow to the child.
- Provide heat to best match human body temperature which is more comfortable for the child rather than cold dry air
- Provide humidification to reduce risk of dry nasal passages
What is being investigated?
Comparing High Flow therapy with standard oxygen therapy delivery on children 1-4 years (up to but excluding the 5th birthday) with common respiratory illnesses and investigate which therapy has the reduced hospital length of stay.
Which patients can take part?
Children 1-4 years of age (up to but excluding their 5th birthday) can be included in this study.
What does the PARIS II study involve for the children in the trial?
Children who are enrolled into this study will be allocated to a treatment arm that is standard therapy in the participating hospital. Children included are those who are 1-4 years of age (up to but excluding their 5th birthday) who have Acute Hypoxemic Respiratory Failure (AHRF) or more commonly known as common respiratory illnesses such as pneumonia and asthma.
Children will present to the emergency department and be assessed and treated by the medical and nursing team. If the child needs oxygen they will be given oxygen. If the child is admitted to hospital, the clinical staff will test if the child still requires oxygen by removing it and testing their saturations level. If it is deemed low for the child the staff will then randomise the child into the study and apply the allocated treatment arm.
The two treatment arms are:
- Standard oxygen therapy via nasal cannula or face mask.
- High flow therapy via nasal cannula which is heated and humidified and provides higher flows to the child.
The parent/guardian will be approached during the child’s hospital stay at some point regarding consent for the study team to obtain the physiological values such as heart rate, respiratory rate of their child.
If at any time the parent/guardian wishes to opt out of the study they can do so by discussing this with their medical officer. This will in no way change the care that your child receives.
Investigating Nasal High Flow therapy in children with respiratory disease – PARIS II Trial
Worldwide, the respiratory distress associated with pneumonia and other causes remains the leading cause of death in children. In Australia, 34% of intensive care admissions for children are due to respiratory disease, which encompasses viral infections representing 19%, asthma 7% and pneumonia 8%.
The uptake of nasal high flow (NHF) therapy treatment in infants and children with acute respiratory failure is increasingly used in Australia and New Zealand with a need for greater evidence. This PARIS II trial will investigate the role of NHF therapy in children with acute hypoxemic respiratory failure.
Our proposed study encompasses these three key elements: we intend to test if early use of NHF therapy reduces the risk of progression of respiratory distress requiring mechanical ventilation and reduces the length of stay and burden of the disease.
The rationale of this study is based on the global burden of respiratory disease and an urgent need to test if NHF therapy can reduce health care costs and potentially mortality rates in under resourced countries.
Specifics of trial
The aim of the study is to investigate in a randomised controlled trial performed in children aged 1-4 years (up to but excluding 5th birthday) presenting with acute hypoxemic respiratory failure if the early use of Nasal High Flow therapy has a lower treatment failure rate compared to standard oxygen therapy with a reduced hospital length of stay.
We hypothesise that:
- Children with acute hypoxemic respiratory failure treated with early use of NHF therapy have a reduced hospital length of stay than standard oxygen therapy.
- Children with acute hypoxemic respiratory failure treated with early use of NHF therapy have a reduced length of oxygen therapy than standard oxygen therapy
- Children with acute hypoxemic respiratory failure treated with early use of NHF therapy have a reduced intensive care admission rate, with reduced need for mechanical respiratory support such as non-invasive or invasive mechanical ventilation.
- Children presenting with obstructive airway disease show a greater benefit of the early use of NHF therapy compared with standard oxygen therapy.
- Early use of NHF therapy compared to standard oxygen therapy leads to reduced health care costs per hospital admission in children with AHRF.
A multicentre blinded Phase III randomised controlled trial.
The participating centres will be enrolling patients to capture a total of 1542 patients with a 1:1 Ratio randomisation.
Outcomes, significance and innovation
The clinical importance of this study is to create high-grade evidence for the use of NHF therapy in children, an important knowledge gap that may have the potential to change worldwide standard clinical practice and reduces the burden on the health care system. Thus our proposed NHF therapy study will be a landmark trial to test the effect of a major change in the respiratory care path for AHRF in children.
- Infants and children aged 1-4 years (up to but excluding 5th birthday) presenting with AHRF.
- Require hospital admission despite initial assessment and therapy.
- Have an ongoing oxygen requirement (SpO2 <90/92% in room air – dependant on hospital SpO2 threshold) at the time of randomisation – it is preferential to observe patient in room air for up to 10 mins if safe to do so.
- Have a persistent tachypnoea of ≥ 35 resp/min at the time of randomisation.
- Oxygen requirement and therapy in the emergency department existed for longer than 4 hours prior to inclusion (excludes oxygen given in ambulance or other hospital)
- Previous use of high flow during this illness episode
- Upper airway obstruction
- Craniofacial malformations
- Critically ill infants requiring immediate higher level of respiratory support i.e. NIV or invasive ventilation, low level of consciousness OR
- Critically ill with immediate need for intubation or non-invasive ventilation with the need of closer observation in ICU
- Basal skull fracture
- Cyanotic Heart Disease (eg. Blue baby, expected normal saturation 60-94%)
- Home Oxygen therapy
- Apnoeas (defined as requiring respiratory support such as NIV or mechanical ventilation)
- Cystic Fibrosis
- Oncology patients
- Palliative Care Patients
- Child protection case (eg. Non-accidental injury, SCAN/CYFS)
Study flow diagram
Escalation of care with or without change in therapy in both intervention arms. At any time there is a change in oxygen therapy (standard oxygen to NHF therapy or NHF therapy to standard oxygen) data on reasoning for the change in therapy will be captured. Similarly if there is an escalation of care to intensive care or high dependency unit the clinical criteria will be recorded to inform the decision making process.
The primary outcome is defined as the treatment failure of the randomised therapy, requiring change in therapy or escalation of care to intensive care/higher level of care.
Secondary outcome measures
- To demonstrate whether the early use of NHF therapy leads to a reduced length of stay in hospital
- To perform a subgroup analysis for children with obstructive/reactive airway disease
- To demonstrate whether the early use of NHF therapy reduces health care costs.
- To investigate the efficacy of NHF therapy in the group of children with obstructive (reactive) airway disease and non-obstructive lung disease (pneumonia).
- To determine the proportion of children requiring transfer to a tertiary hospital
- To determine the proportion of patients requiring escalation of therapy such as non-invasive or invasive ventilation
- To measure the side effects of NHF therapy compared with standard oxygen therapy
Definition of AHRF
Children presenting with increased work of breathing, oxygen requirement to maintain SpO2 ≥90/92% (dependent on hospitals current threshold for applying oxygen therapy) and an increased respiratory rate (age dependent). The syndrome of AHRF represents an array of clinical diagnoses such as pneumonia, pneumonitis, acute lower respiratory tract infection, reactive airways (asthma) including bronchiolitis. For the purpose of this study there will be two groups of patients investigated with a pragmatic and point of care definition, which includes:
- Wheeze – (obstructive) and reactive airway disease with an oxygen requirement during admission to hospital.
- Absent wheeze – (non-obstructive) and parenchymal lung disease with an oxygen requirement during admission to hospital.
Escalation of care, or change in therapy
Children who are randomised to standard oxygen therapy (control) or NHF therapy and meet the escalation criteria may then escalate to a different therapy as per the attending physician or be directly admitted to ICU. The alternate therapy may be standard oxygen therapy, NHF therapy, CPAP, BiPAP or mechanical ventilation for either randomised therapy group. This decision is at the discretion of the clinician. Children who are randomised to NHF therapy may at times meet the escalation criteria, but improve on standard oxygen therapy. This change in therapy can occur at the discretion of the clinician.
The following 16 centres (Emergency Departments and Paediatric Departments) have agreed to participate in the study:
- Queensland Children’s Hospital, Qld
- Royal Children’s Hospital, Melbourne, Victoria
- Gold Coast University Hospital, Qld
- Redcliffe Hospital, Qld
- The Prince Charles Hospital, Qld
- Sunshine Coast University Hospital (SCUH), Qld
- Ipswich Hospital, Qld
- Toowoomba Hospital, Qld
- The Tweed Hospital, NSW
- Monash Health, Victoria
- Townsville Hospital, Qld
- Caboolture Hospital, Qld
- Perth Children’s Hospital, WA
- John Hunter Children’s Hospital, NSW
- Starship Children’s Health, Auckland
- KidzFirst, Middlemore Hospital, South Auckland
Collaborators and sponsors
We are fortunate to be supported by funding grants including:
- National Health and Medical Research Council, Australia
- Thrasher Foundation and Children’s Hospital Foundation, USA
- Children’s Health Foundation, Qld, Australia
- Perth Children’s Hospital Foundation, WA, Australia
Our collaborators include
- The University of Queensland and the
- Paediatric Emergency Departments International Collaborative group (PREDICT)
Our collaborators include
- The University of Queensland
- PREDICT (Paediatric Emergency Departments International Collaborative group)