Clinical trial NCT02612415: FIRST-line Support for Assistance in Breathing in Children (FIRST-ABC) Feasibility Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypoxia
Respiratory Acidosis
Moderate/Severe Respiratory Distress
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: Barts & The London NHS Trust
name: Intensive Care National Audit & Research Centre
First posted: 2015-11-23
Enrollment: 121
Sex: ALL
Minimum age (years): 36
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Eligible patients will fall into one of two groups:

Group A (Step-up)

1. Age \>36 weeks corrected gestational age and \<16 years, AND
2. Deemed to require non-invasive respiratory support by the treating clinician for an acute illness, AND
3. 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)

1. Age \>36 weeks corrected for gestation and \<16 years, AND
2. 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:

1. 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
2. Tracheostomy in place
3. Pre-existing air-leak syndrome (pneumothorax/pneumomediastinum)
4. Midfacial/craniofacial anomalies (unrepaired cleft palate, choanal atresia) or had recent craniofacial surgery
5. Agreed limitation of intensive care treatment plan in place ('not for intubation')
6. On domiciliary non-invasive ventilation prior to PICU admission
7. Managed on either HFNC and/or CPAP (or other form of non-invasive ventilation such as BiPAP) in the preceding 24 hours
8. Previously recruited to this study during the same PICU admission
9. Cannot be treated with HFNC

   * Unavailability of appropriate sized nasal prongs
   * Unavailability of HFNC device
10. Cannot be treated with CPAP

    * Unavailability of right size of face mask, prong or other patient interface
    * Unavailability of CPAP device

Primary outcomes:
measure: Number of eligible patients in Group A (step-up) and Group B (step-down)
timeFrame: Baseline
measure: Number of parents/guardians who refuse prospective or deferred consent
timeFrame: Through study completion, an average of 24 hours
measure: Randomising at least 50% of eligible patients
timeFrame: Baseline
measure: Proportion of patients adherent to the study treatment
timeFrame: Through study completion, an average of 72 hours
measure: Mean COMFORT score
timeFrame: 72 hours
measure: Number of parents completing the Parental Stressor Scale: PICU (PSS:PPICU)
timeFrame: 24 hours
Secondary outcomes:
measure: Proportion of children randomised to the intervention or control who need intubation (Group A) or re-intubation (Group B)
timeFrame: 72 hours
measure: 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
timeFrame: 72 hours
measure: 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
timeFrame: 28 days
measure: Improvement in oxygenation, partial pressure of carbon dioxide (pCO2) levels, heart rate, respiratory rate, and work of breathing
timeFrame: 24 hours
measure: Length of PICU and hospital stay, length of invasive ventilation, length of non-invasive support, ventilator-free days at day 28
timeFrame: through study completion, an average of 28 days
measure: Mortality at PICU discharge and at hospital discharge
timeFrame: through study completion, an average of 28 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Consultant in Paediatric Intensive Care & Retrieval Children's Acute Transport Service (CATS)
name: Padmanabhan Ramnarayan
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramnarayan P, Lister P, Dominguez T, Habibi P, Edmonds N, Canter RR, Wulff J, Harrison DA, Mouncey PM, Peters MJ; United Kingdom Paediatric Intensive Care Society Study Group (PICS-SG). FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care. Crit Care. 2018 Jun 4;22(1):144. doi: 10.1186/s13054-018-2080-3.
citation: Ramnarayan P, Lister P, Dominguez T, Habibi P, Edmonds N, Canter R, Mouncey P, Peters MJ. FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children. BMJ Open. 2017 Jun 12;7(6):e016181. doi: 10.1136/bmjopen-2017-016181.