Prone Position in Acute Bronchiolitis (PROPOSITIS)

Effect of Prone Position on the Use of Non-invasive and Invasive Ventilation in Infants With Moderate to Severe Acute Bronchiolitis

Acute viral bronchiolitis is the leading cause of community-acquired acute respiratory failure in developed countries (20 000 to 30 000 hospitalizations each year in France). Between 5% and 22% of these children are hospitalized in a critical care unit to benefit from a respiratory support.

Non-invasive ventilation, in particular the nasal Continuous Positive Airway Pressure (nCPAP), reduces the work of breathing in children with bronchiolitis and is associated with decreased morbidity and hospitalization costs compared with invasive ventilation. Nowadays, this technique is considered as the gold standard in the pediatric intensive care units (PICU) in France. High Flow Nasal Cannula (HFNC) has been proposed as an alternative to the nCPAP because of its better tolerance and simplicity of implementation. However, the proportion of failure remains high (35 to 50%), providing only a partial response to the care of these children, especially prior to the PICU.

In a physiological study (NCT02602678, article published), it has been demonstrated that prone position (PP) decrease, by almost 50%, the respiratory work of breathing and improve the respiratory mechanics in infants hospitalized in intensive care units for bronchiolitis.

Investigators hypothesize that prone position, during High Flow Nasal Cannula (HFNC), would significantly reduce the use of non-invasive ventilation (nCPAP and others) or invasive ventilation, as compared to supine position during HFNC, in infants with moderate to severe viral bronchiolitis.

Study Overview

• Status: Recruiting
• Conditions: Acute Viral Bronchiolitis
• Intervention / Treatment: Procedure: Supine position (SP); Procedure: Prone position (PP)

• Study Type: Interventional
• Enrollment (Anticipated): 452
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florent BAUDIN, Dr; Phone Number: +33 04 72 12 97 35; Email: florent.baudin@chu-lyon.fr
• Study Contact Backup: Name: Tiphanie GINHOUX; Phone Number: +33 04 27 85 77 23; Email: tiphanie.ginhoux@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Réanimation pédiatrique et unité de surveillance continue - Hôpital Femme Mère Enfant - Hospices Civils de Lyon
    • Contact: Florent BAUDIN, Dr; Phone Number: +33 04 72 12 97 35; Email: florent.baudin@chu-lyon.fr
    • Contact: Tiphanie GINHOUX; Phone Number: +33 04 27 85 77 23; Email: tiphanie.ginhoux@chu-lyon.fr
    • Principal Investigator: Florent BAUDIN, Dr
  • Caen, France, 14000
    • Not yet recruiting
    • CHU de Caen, Service de réanimation et surveillance continue pédiatrique
    • Contact: BROSSIER David; Email: brossier-d@chu-caen.fr
    • Principal Investigator: BROSSIER David
  • Chambéry, France, 73000
    • Recruiting
    • CH CHAMBERY Unité de surveillance continue pédiatrique
    • Contact: Corinne PAGET; Phone Number: +33 04 79 96 61 60; Email: Corinne.Paget@ch-metropole-savoie.fr
  • Dijon, France, 21079
    • Not yet recruiting
    • Hôpital d'Enfants CHU de Dijon Service de réanimation pédiatrique
    • Contact: NALLET-AMATE Megan; Email: megan.nallet-amate@chu-dijon.fr
    • Principal Investigator: NALLET-AMATE Megan
  • Gleizé, France, 69400
    • Recruiting
    • CH VILLEFRANCHE Service de pédiatrie néonatologie
    • Contact: Marie TOCHON TEIXEIRA; Phone Number: +33 04 74 09 28 39; Email: MTochon@lhopitalnordouest.fr
  • La Tronche, France, 38700
    • Recruiting
    • CHU GRENOBLE Service de réanimation pédiatrique Hôpital Couple Enfant
    • Contact: Guillaume MORTAMET; Phone Number: +33 04 76 76 55 03; Email: gmortamet@chu-grenoble.fr
  • Montpellier, France, 34295
    • Recruiting
    • CHU MONTPELLIER Service de réanimation pédiatrique
    • Contact: Christophe MILESI; Phone Number: +33 04 67 33 66 09; Email: c-milesi@chu-montpellier.fr
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes Unité de surveillance continue pédiatrique Hôpital mère-enfant
    • Contact: Jean Eudes PILOQUET; Email: piloquet.jeaneudes@gmail.com
  • Nice, France, 06200
    • Recruiting
    • CHU LENVAL NICE Service de réanimation pédiatrique
    • Contact: Mickael AFFANETI; Phone Number: +33 04 92 03 04 08; Email: afanetti.m@pediatrie-chulenval-nice.fr
  • Paris, France, 75015
    • Recruiting
    • Hôpital Necker Enfant Malade, Paris Service de Réanimation et surveillance continue médicochirurgicales
    • Contact: Sylvain RENOLLEAU; Phone Number: +33 01 44 49 56 67; Email: sylvain.renolleau@aphp.fr
  • Saint-Priest-en-Jarez, France, 42270
    • Recruiting
    • CHU SAINT-ETIENNE Service de réanimation pédiatrique
    • Contact: François BARRIERE; Phone Number: +33 04 77 82 83 85; Email: francois.barriere@chu-st-etienne.fr
  • Vandœuvre-lès-Nancy, France, 54500
    • Not yet recruiting
    • CRHU Nancy Réanimation Pédiatrique Spécialisée
    • Contact: WIEDEMANN Arnaud; Email: a.wiedemann-fode@chru-nancy.fr
    • Principal Investigator: WIEDEMANN Arnaud
  • Épagny, France, 74370
    • Recruiting
    • CH ANNECY GENEVOIS Unité de surveillance continue pédiatrique
    • Contact: Clémence JARASSE; Phone Number: +33 04 50 63 63 24; Email: cjarrasse@ch-annecygenevois.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 10 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infant under 6 months
• Hospitalized in critical care unit (continuous monitoring unit or intensive care unit)
• With a clinical diagnosis of acute viral bronchiolitis (criterion of the American Academy of Pediatrics 2014)
• m-WCAS score ≥ 3 and / or hypercapnic acidosis with pH <7.35 and pCO2> 50mmHg (6.7 kPa)
• Informed consent signed by at least one of the parents with oral consent of the other parent (and / or legal guardian) recorded in the medical file.

Exclusion Criteria:

• Infant admitted with criteria for invasive or non-invasive ventilation (hypercapnic acidosis with pH <7.25 without ventilatory support and/or hypoxia with impossibility of maintaining SpO2> 92% whatever the FiO2 and/or more than 3 significant apneas per hour and/or severe consciousness disorder)
• Patient already positioned in the prone position before randomization
• Significant comorbidities with a history of respiratory pathology (bronchodysplasia with ventilatory support), Ear Nose and Throat pathology (pharyngolaryngomalacia) or neuromuscular and / or hemodynamically significant congenital heart disease.
• Contraindication to Prone position : recent abdominal surgery (laparoschisis or omphalocele) or recent sternotomy
• Patient who is not affiliated (or does not benefit from) to a national social security system

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Supine position (SP); Supine position (SP) combined with HFNC	Procedure: Supine position (SP); Infants under high flow nasal cannula (HFNC) will be positioned in the supine position. Patients may be positioned temporarily in lateral position between periods of supine position to limit ventilatory disorders, as it is usually done in critical care units during bronchiolitis.
Experimental: Prone position (PP); Prone position (SP) combined with HFNC	Procedure: Prone position (PP); Infants under high flow nasal cannula (HFNC) will be placed in the prone position during at least 24 hours over the first 48 hours. The positioning will be standardized (chest on the bed plan and abdomen cleared) and children should be placed in the prone position immediately after randomization. Patients may be positioned temporarily in lateral position between periods of prone position to limit ventilatory disorders, as it is usually done in critical care units during bronchiolitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of ventilated children in each of the 2 groups	Indications for the use of ventilation (invasive or non-invasive ventilation) will be standardized in both groups (based on the interregional protocol for the management of bronchiolitis): Clinical aggravation defined by an increase ≥ 1 point of the m-WCAS score; Persistence of hypercapnic acidosis with pH ≤7.30 and pCO2≥ 8 kPa or FiO2> 60% under HFNC at 2 L/kg/min; More than 2 significant apneas per hour (apnea with desaturation <90% and / or bradycardia <90 / min); Consciousness disorder Anytime over the first 3 days after inclusion	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of failure	Failure is defined as: HFNC failure (composite failure criterion validated by an independent committee); worsening of mWCAS score ≥ 1 point; hypercapnic acidosis (pH ≤7.30 and pCO2≥8kPa); significant apnea (apnea with desaturation <90% and / or bradycardia <90/min) Anytime over the first 3 days after inclusion	3 days
Causes of failure	Failure is defined as: HFNC failure (composite failure criterion validated by an independent committee); worsening of mWCAS score ≥ 1 point; hypercapnic acidosis (pH ≤7.30 and pCO2≥8kPa); significant apnea (apnea with desaturation <90% and / or bradycardia <90/min) Anytime over the first 3 days after inclusion	3 days
Duration of ventilation	Duration of ventilation (high flow nasal cannula, invasive, non-invasive) in hours. This data will be collected at critical care unit discharge.	maximum 3 months
Length of stay	Length of stay in days. This data will be collected at hospital discharge.	maximum 3 months
Oxygenation evaluation	Evolution of FiO2 and SpO2/FiO2 ratio between inclusion and H2.	2 hours
Oxygenation evaluation	Evolution of FiO2 and SpO2/FiO2 ratio between inclusion and H12.	12 hours
Oxygenation evaluation	Evolution of FiO2 and SpO2/FiO2 ratio between inclusion and H24.	24 hours
Tolerance evaluation	Proportion of skin lesions, vomiting/regurgitation and exclusive enteral nutrition. This data will be collected at critical care unit discharge.	maximum 3 months
Variation EDIN score (Scale of pain and discomfort of the newborn) between inclusion and after 2 hours	Scale ranges to 0 from 15 and is a combination of criteria: Face: Relaxed=0 to Permanent tightness or prostrate face,frozen or purple face=3; Body: Relaxed=0 to Permanent agitation,tightness of extremities and stiffness of limbs or very poor and limited motor skills with fixed body=3; Sleep:Easily, extended and calm=0 to No sleep=3; Relationship:Smile to the angels,smile answer,attentive to the listening=0 to Refuses contact,no relationship possible,howl or moan without any stimulation=3; Comfort: Do not need comfort=0 to Inconsolable,desperate sucking=3	2 hours
Evaluation of the feasibility of maintaining the position	Proportion of children in the prone position repositioned definitively in the supine position before performing the cumulative 24 hours of prone position, cumulative hours of prone position in the first 48 hours	48 hours

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2021
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Randomized controlled trial; noninvasive ventilation; Prone position; high flow nasal cannula; viral bronchiolitis
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Bronchiolitis, Viral
• Other Study ID Numbers: 69HCL19_0333

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