FIRST-line Support for Assistance in Breathing in Children (FIRST-ABC) Feasibility Study

Study Overview
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Brief Summary
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A feasibility study to inform the design and conduct of a randomised controlled trial of high flow nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in critically ill children

Detailed Description
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Breathing support is the most common intervention provided to critically ill children in a paediatric intensive care unit (PICU). Although invasive breathing support (delivered through a tracheal tube) is lifesaving, concerns regarding its risks (infection and lung damage) have prompted greater use of non-invasive respiratory support (NRS). However, there is little scientific evidence to guide PICU clinicians on the comparative effectiveness of the commonly used modes of NRS. In this feasibility study, the investigators are testing whether it is possible to conduct a randomised clinical trial comparing two modes of NRS: continuous positive airway pressure (CPAP), which has been used for over two decades, and high flow nasal cannula (HFNC), a newer method of respiratory support. It is not known for sure how useful HFNC is in critically ill children because there is no published research comparing it with CPAP. However, since HFNC is easier to use and better tolerated by children, many hospitals are now using HFNC instead of CPAP. Before HFNC is widely adopted, a clinical trial to establish its role in the management of critically ill children is urgently needed. As part of this study, the investigators will randomly allocate children deemed to require NRS by their treating clinician to either HFNC or CPAP. The investigators will mainly assess whether sufficient number of children can be recruited to the trial, whether clinicians are willing to randomise children, and test the proposed treatment pathways for CPAP and HFNC. The trial will run over six months, and recruit 120 sick children from three National Health Service (NHS) hospitals. Consent will be sought from parents/guardians for their children to be included in the study, usually before CPAP or HFNC is started, unless emergency life-saving treatment is required, in which case consent will be deferred until there is more time to discuss the study with parents/guardians.

Official Title
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FIRST-ABC Feasibility Study: Feasibility Study for a Randomised Trial of High Flow Nasal Cannula (HFNC) Versus Continuous Positive Airway Pressure (CPAP) for Non-invasive Respiratory Support in Critically Ill Children

Conditions
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Hypoxia, Respiratory Acidosis, Moderate/Severe Respiratory Distress

Intervention / Treatment
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* Device: Treatment strategy: Non-invasive respiratory support delivered via high flow nasal cannula
* Device: Treatment strategy: Non-invasive respiratory support delivered via continuous positive airway pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients will fall into one of two groups: Group A (Step-up) Age >36 weeks corrected gestational age and <16 years, AND Deemed to require non-invasive respiratory support by the treating clinician for an acute illness, AND Satisfies one or more of the following criteria: Hypoxia (oxygen saturation <92% in fraction of inspired oxygen (FiO2) >0.40, or equivalent). FiO2 of 0.40 roughly equates to standard unhumidified nasal cannula oxygen delivered at 6 L/min or oxygen delivered via facemask without a rebreather bag at 6-10 L/min. Acute respiratory acidosis (pH <7.3 with a concomitant pCO2 >6.5 kPa) Moderate respiratory distress (use of accessory muscles, subcostal and intercostal recession, tachypnoea for age, grunting) Group B (Step-down) Age >36 weeks corrected for gestation and <16 years, AND Deemed to require non-invasive respiratory support by the treating clinician after extubation, following a spell of invasive ventilation Either immediately after extubation as a 'planned' procedure, irrespective of clinical condition ('planned') OR Prompted by deterioration in clinical condition within 72 hours after extubation ('rescue'). Clinical parameters to assess the need for NRS in this situation will be similar to point 3 in Group A. Exclusion Criteria: Deemed by the treating clinician to require immediate intubation/invasive ventilation due to severe hypoxia, acidosis and/or respiratory distress, upper airway obstruction or recurrent apnoeas Tracheostomy in place Pre-existing air-leak syndrome (pneumothorax/pneumomediastinum) Midfacial/craniofacial anomalies (unrepaired cleft palate, choanal atresia) or had recent craniofacial surgery Agreed limitation of intensive care treatment plan in place ('not for intubation') On domiciliary non-invasive ventilation prior to PICU admission Managed on either HFNC and/or CPAP (or other form of non-invasive ventilation such as BiPAP) in the preceding 24 hours Previously recruited to this study during the same PICU admission Cannot be treated with HFNC Unavailability of appropriate sized nasal prongs Unavailability of HFNC device Cannot be treated with CPAP Unavailability of right size of face mask, prong or other patient interface Unavailability of CPAP device

Ages Eligible for Study
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Minimum Age: 36 Weeks
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High flow nasal cannula (HFNC)<br>Heated humidified high flow nasal cannula therapy delivered at 2 L/kg/min gas flow rate (for children older than 10 kg in weight, an additional 0.5 L/kg/min per kilogram over 10 kg). Any approved device can be used to deliver HFNC | Device: Treatment strategy: Non-invasive respiratory support delivered via high flow nasal cannula<br>* A heated, humidified, HFNC device will be used to deliver a gas flow rate of 2 L/kg/min for the duration that the patient needs non-invasive respiratory support<br>|
| Active Comparator: Continuous positive airway pressure (CPAP)<br>Continuous positive airway pressure delivered using any interface (hood, mask or prongs) | Device: Treatment strategy: Non-invasive respiratory support delivered via continuous positive airway pressure<br>* CPAP will be provided using a set expiratory pressure of 6-8 cm water (H2O) pressure for the duration that the infant needs non-invasive respiratory support<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of eligible patients in Group A (step-up) and Group B (step-down) |  | Baseline | 
| Number of parents/guardians who refuse prospective or deferred consent |  | Through study completion, an average of 24 hours | 
| Randomising at least 50% of eligible patients |  | Baseline | 
| Proportion of patients adherent to the study treatment |  | Through study completion, an average of 72 hours | 
| Mean COMFORT score |  | 72 hours | 
| Number of parents completing the Parental Stressor Scale: PICU (PSS:PPICU) |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children randomised to the intervention or control who need intubation (Group A) or re-intubation (Group B) |  | 72 hours | 
| Proportion of children randomised to the intervention or control who fail the assigned treatment and require either crossover or escalation to other forms of ventilation |  | 72 hours | 
| Number of children who experience pre-specified adverse events (pneumothorax, pneumomediastinum, nasal or facial trauma, abdominal distension, nosocomial infection) during the period they are receiving non-invasive respiratory support |  | 28 days | 
| Improvement in oxygenation, partial pressure of carbon dioxide (pCO2) levels, heart rate, respiratory rate, and work of breathing |  | 24 hours | 
| Length of PICU and hospital stay, length of invasive ventilation, length of non-invasive support, ventilator-free days at day 28 |  | through study completion, an average of 28 days | 
| Mortality at PICU discharge and at hospital discharge |  | through study completion, an average of 28 days |