High Flow Nasal Cannula in Children With Status Asthmaticus (CANULASTHM)

High Flow Nasal Cannula Versus Standard Oxygen Therapy in Children With Status Asthmaticus: a Randomized Controlled Trial

In France, over 2.5 million people suffer from asthma, including one-third of children. This is the chronic respiratory disease leading to the highest rate of hospitalization. The conventional oxygen delivery means in children are the non-rebreather face mask or low flow nasal cannula (standard oxygen therapy - SOT). New non-invasive ventilatory support systems such as High Flow Nasal Cannula (HFNC) are emerging. These are nasal cannulas allowing the delivery of a high air (or oxygen) flow, exceeding the inspiratory flow of patients with acute respiratory failure, allowing to deliver a slight positive expiratory pressure while ensuring humidification and warming of the airways. Aerosol administration is also possible with excellent efficiency and without interrupting respiratory assistance. Physiological data and clinical studies in other pathologies suggest the interest of this technique during the asthma attack, but no comparative study currently exists in this indication. The HFNCs could have their place upstream of Non Invasive Ventilation (NIV), thus replacing non-rebreather face mask sometimes not tolerated by the children. The investigators's hypothesis is that HFNCs could improve patients' health faster, reduce the use of other ventilatory assistance (NIV, invasive ventilation) and reduce the duration of hospitalization in intensive care units or continuous monitoring units (CMU).

Study Overview

• Status: Completed
• Conditions: Status Asthmaticus
• Intervention / Treatment: Device: HFNC; Device: Standard Oxygen Treatment

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robin Pouyau, Dr; Phone Number: +33 472 129 747; Email: robin.pouyau@chu-lyon.fr
• Study Contact Backup: Name: Tiphanie Ginhoux; Phone Number: +33 427 857 723; Email: tiphanie.ginhoux@chu-lyon.fr

Study Locations

• France
  • Bron, France
    • Hôpital Femme-Mère-Enfant
  • Dijon, France
    • CHU de Dijon
  • Grenoble, France
    • CHU de Grenoble Alpes
  • Le Kremlin Bicêtre, France
    • Hôpital Bicêtre
  • Marseille, France
    • Hôpital Timone 2
  • Metz-Tessy, France
    • Ch Annecy Genevois
  • Montpellier, France
    • CHU Arnaud de Villeneuve
  • Nantes, France
    • CHU de Nantes
  • Nice, France
    • CHU Lenval
  • Paris, France
    • Hôpital Necker Enfants Malades
  • Paris, France
    • Hôpital Robert Debré
  • Paris, France
    • Hôpital Armand Trousseau
  • Strasbourg,, France
    • CHU Strasbourg,
  • Villefranche sur Saône, France
    • CH Villefranche sur Saône,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 6 months and <18 years old

• Hospitalized in PICU with status asthmaticus defined by

  1. a PRAM score > 7 with no response at H2 to the conventional treatment according to the GINA (Global Initiative for Asthma guidelines) protocol: Oxygen therapy, Continuous nebulization of beta2 agonist for at least one hour then every hour, Oral or intravenous corticosteroid (ie methylprednisolone 2mg/kg/j)
  2. or with hypercapnic acidosis (pCO2 > 45 mmHg and pH < 7,35)
• Informed consent signed by at least on parent or legal guardians prior to inclusion and oral consent of the other parent if absent

Exclusion Criteria:

• Non-corrected congenital heart disease, or neuromuscular disease, or chronic respiratory disease (pulmonary or bronchial fibrosis, cystic fibrosis), or ENA disease (laryngo or tracheo malacia), scoliosis or chronic metabolic disease
• Need for non-invasive or invasive ventilation (Glasgow comas scale <8, hemodynamic instability, refractory hypoxemia, cardiac arrest)
• Pneumothorax confirmed on the X-ray
• No national health coverage

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HFNC group	Device: HFNC; Oxygen therapy will be delivered through high flow nasal cannulas. Aerosol treatments will be administered through a vibrating mesh nebulizer directly connected to the circuit (aerogen®). The airvo® system (Fisher & Peykel Healthcare, Auckland, New Zealand) will be used as the high flow cannula system in the study. Cannula size will be tailored to the child according to the manufacturer's recommendations. The gas flow will be adjusted according to the child's weight in a predefined chart. FiO2 will be adjusted to allow for a SpO2 >92%. All the patients, regardless of their treatment failure status, will be evaluated at H2, H6, H12 and H24 to monitor their evolution (evaluation of the standard parameters, consciousness, PRAM (Pediatric Respiratory Assessment Measure) score, pain assessment by the FLACC (Face Legs Activity Cry Consolability) score). .
Other: Standard Oxygen Therapy group (STO group)	Device: Standard Oxygen Treatment; Children will receive supplemental oxygen as commonly delivered through a non-rebreather face mask or low flow nasal cannula (standard oxygen treatment) and beta2 agonist aerosol via vibrating mesh nebulizer (aerogen®) according to the procedures usually used in the unit and according to the GINA (Global Initiative for Asthma) protocol. This group is the standard treatment group and is therefore the control group. All the patients, regardless of their treatment failure status, will be evaluated at H2, H6, H12 and H24 to monitor their evolution (evaluation of the standard parameters, consciousness, PRAM score, pain assessment by the FLACC score). The use of adjuvant therapies (magnesium sulfate, salbutamol IVSE, and ipratropium bromide) will remain at the discretion of the physician in charge of the child and will be evaluated as a secondary criterion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with first line treatment Failure as defined below in the first 24 hours	First line treatment Failure in the first 24 hours is defined as: Occurrence or worsening of hypercapnic acidosis (pH<7.35 with pCO2>45 mmHg); Or worsening of PRAM score (>=2 from baseline); Or SpO2<92% with maximal flow of oxygen depending on age in the group standard oxygen therapy or with FiO2 > 60% associated with a flow between 1 and 3L/Kg/min in the HFNC group; Or occurrence or worsening of the level of consciousness with Glasgow coma scale < 12; Or the need of invasive or noninvasive ventilation (Glasgow coma scale<8, hemodynamic instability, refractory hypoxemia) at any time during the first 24 hours	up to hour 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients requiring noninvasive ventilation (NIV)		month 1
Number of Patients requiring invasive ventilation (IV).		month 1
Duration of invasive ventilation (IV).	Duration in hours	month 1
Duration of noninvasive ventilation (NIV)	Duration in hours	month 1
Comfort assessed by the FLACC score		up to hour 24
Duration of supplemental oxygen therapy (in hours)		month 1
Time from inclusion to restoration of a PRAM score < 8 (in hours).		month 1
Time from inclusion to blood gas normalization (pCO2<45 mmHg and pH>7.35) if available (hours)		month 1
Cumulative dose of treatments (salbutamol, corticosteroid magnesium sulfate)	in milligram during PICU stay	month 1
total number of hours of PICU stay		month 1

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Robin Pouyau, Dr, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2018
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: May 2, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: children; HFNC; status asthmaticus
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Status Asthmaticus
• Other Study ID Numbers: 69HCL17_0035; IDRCB (Registry Identifier: 2022-A02601-42)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No