Safe, Effective and Cost-Effective Oxygen Saturation Targets for Children and Adolescents With Respiratory Distress: a Randomized Controlled Trial (OxyKids)

The goal of this clinical trial is to find out at which lower limit for saturation (amount of oxygen in the blood) we can best give extra oxygen to children that have been admitted for shortness of breath. We hope to accomplish a shorter period of illness for these children and that they can be discharged home earlier. Participants will receive supplemental oxygen if their blood oxygen levels are below 88% or below 92%. After admission, (parents of) participating children will fill out questionnaires. We will compare the two groups on their hospitalization duration and recovery.

In other words, is it better to maintain a lower limit of 88% saturation or a lower limit of 92% in children admitted for shortness of breath?

Study Overview

• Status: Recruiting
• Conditions: Bronchiolitis; Lower Respiratory Tract Infection; Bronchial Hyperreactivity
• Intervention / Treatment: Other: Oxygen saturation threshold

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sam Louman, MD; Phone Number: +3123-2241645; Email: slouman@spaarnegasthuis.nl

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate Ziekenhuis
    • Contact: Mirjam Scheffer; Phone Number: +31880057782; Email: mscheffer@rijnstate.nl
    • Principal Investigator: Mirjam Scheffer
  • Arnhem, Netherlands
    • Recruiting
    • Canisius Wilhelmina Ziekenhuis
    • Contact: Marianne L Brouwer; Phone Number: +31243658146; Email: m.l.brouwer@cwz.nl
    • Principal Investigator: Marianne L Brouwer
  • Breda, Netherlands
    • Recruiting
    • Amphia Ziekenhuis
    • Contact: Anja Vaessen-Verberne; Phone Number: +31765951012; Email: avaessen-verberne@amphia.nl
    • Principal Investigator: Anja Vaessen-Verberne
  • Groningen, Netherlands
    • Recruiting
    • Martini Ziekenhuis
    • Contact: Arvid Kamps; Phone Number: +31505245245; Email: akamps@martini.nl
    • Principal Investigator: Arvid Kamps
  • Hilversum, Netherlands
    • Recruiting
    • Tergooi Ziekenhuis
    • Contact: Caroline Kosterink-Brackel; Phone Number: +31887531160; Email: ckosterinkbrackel@tergooi.nl
    • Principal Investigator: Caroline Kosterink-Brackel
  • Nieuwegein, Netherlands
    • Recruiting
    • St Antonius Ziekenhuis
    • Contact: Walter Balemans; Phone Number: +31883206300; Email: w.balemans@antoniusziekenhuis.nl
    • Principal Investigator: Walter Balemans
  • Rotterdam, Netherlands
    • Recruiting
    • Franciscus Gasthuis en Vlietland
    • Contact: Ismé de Kleer; Phone Number: +31104616225; Email: i.kleer@franciscus.nl
    • Principal Investigator: Ismé de Kleer
  • Zwolle, Netherlands
    • Recruiting
    • Isala Klinieken
    • Principal Investigator: Jolita Bekhof
    • Contact: Jolita Bekhof; Phone Number: +31886245050; Email: j.bekhof@isala.nl
  • Noord-Holland
    • Haarlem, Noord-Holland, Netherlands, 2035 RC
      • Recruiting
      • Spaarne Gasthuis
      • Contact: Annemie LM Boehmer, MD, PhD; Phone Number: +31232240070; Email: aboehmer@spaarnegasthuis.nl
      • Contact: Sam Louman, MD; Phone Number: +31232241645; Email: slouman@spaarnegasthuis.nl
      • Principal Investigator: Annemie LM Boehmer, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 6 weeks to 12 years of age (corrected age for children with gestational age < 37 weeks)
• hospitalized with respiratory distress due to bronchiolitis, viral wheeze or lower respiratory tract infection, as diagnosed by the treating physician. Viral wheeze can only be diagnosed below the age of 6 years.
• requiring supplemental oxygen as per usual care (SpO2 <92% or for treating symptoms of respiratory distress as determined by the treating physician

As respiratory distress in children with an asthma attack is mainly driven by hypoxia, they are at risk of undertreatment in the acute phase of the attack. Therefore, children aged 6-12 years of age with an asthma attack are excluded from this study.

Exclusion Criteria:

• children with, except for the studied diseases, pre-existing cardiopulmonary, neurological or hematological conditions (e.g. congenital thoracic malformation, airway malacia, post infectious bronchiolitis obliterans, childhood interstitial lung disease. primary immune deficiency)
• children born <32 weeks gestational age
• children already included in other studies, which potentially interfere with this study
• children (of parents) without a stable internet connection needed for answering questionnaires
• children previously included in the current study
• considering questionnaires are only available in Dutch and English, children (of parents) with different languages will be excluded.

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: 88% oxygen saturation threshold; Patients in this arm will receive supplemental oxygen when SpO2 falls below 88% or when other clinical symptoms indicate a need for supplemental oxygen.	Other: Oxygen saturation threshold; Oxygen saturation threshold on which supplemental oxygen is decided
Active Comparator: 92% oxygen saturation threshold; Patients in this arm will receive supplemental oxygen when SpO2 falls below 92% or when other clinical symptoms indicate a need for supplemental oxygen.	Other: Oxygen saturation threshold; Oxygen saturation threshold on which supplemental oxygen is decided

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to meeting all discharge criteria	Time in hours from admission to meeting all discharge criteria Discharge criteria include: No need for supplemental oxygen for 4 hours, including a period of sleep for children aged < 2 years; Clinically fit for discharge with normal or minimally increased respiratory rate AND no or mild respiratory distress, as judged by nurses and physicians using the Parshuram et al scoring system, commonly used in Dutch paediatric practice as part of the Pediatric Early Warning Scale].; No need for in-hospital feeding or medication by nasogastric tube (NGT).; No need for in-hospital intravenous treatment.; No need for in-hospital nebulized bronchodilator treatment.; No need for in-hospital treatment with metered dose inhalator inhalations more often than every 3 hours.; No need for high flow delivered by high flow nasal cannula or nasal prongs.	Discharge criteria are checked daily during admission up to discharge (generally a few days up to a week but longer if admission lasts longer) and the time and date at which all discharge criteria have been met will be recorded.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	Time from admission to discharge in hours	During admission
Pediatric Intensive Care Unit (PICU) admissions	Number of PICU admissions per group	During admission
Time on oxygen therapy	Time in hours spent on supplemental oxygen	During admission
Duration of symptoms	Measured as days from admission to having met all of the following criteria: resolution of cough, resolution of dyspnea as indicated by parent, cessation of scheduled bronchodilator use.	from admission to 90 days after discharge
Return to normal health	Measured as days from admission to parent reported normal health. Upon discharge parents/patients are asked to record the last day of illness and report this in the follow-up questionnaires	from admission to 90 days after discharge
Time to return to school/daycare	Measured as days from admission to parent reported return to school/daycare	from admission to 90 days after discharge
Unscheduled health care visits or admissions after discharge	Number of unscheduled visits or admissions up to 28 days after discharge	from admission to 28 days after discharge
Patient quality of life	Measured by digital questionnaire of EQ-5D-Y (modified versions are used in agreement with EuroQol for patients < 4 years)	at discharge, 7, 28 and 90 days follow-up
Overall pediatric health	ICHOM PROMIS Pediatric Global Health set	at discharge, 7, 28 and 90 days follow-up
Parental anxiety	by anxiety items of Hospital Anxiety and Depression Scale	at discharge, 7 and 28 days follow-up
Economic evaluation	The aim of the economic evaluation is to relate the incremental costs of an SpO2 of 88% (intervention) in comparison with an SpO2 of 92% (control) to the incremental health effects. Both a cost-effectiveness analysis (CEA) and a cost-utility analysis (CUA) will be performed from a societal and healthcare perspective	Up to 90 days after discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin type influence	Investigation in to the influence of skin type on safety and effectiveness outcomes	Up to 90 days after discharge
Time spent in 88%-92% window	Time spent in 88%-92% saturation window, measured by extracted continous monitoring data from patients where this is technically a possibility.	recorded at discharge based on monitoring data registered during admission, generally a few days to a week but longer if admission lasts longer.

Collaborators and Investigators

• Sponsor: Spaarne Gasthuis
• Investigators: Principal Investigator: Annmeie LM Boehmer, MD, PhD, Spaarne Gasthuis

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Children; SpO2; Oxygen saturation target
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Respiratory Tract Infections; Bronchiolitis; Bronchial Hyperreactivity
• Other Study ID Numbers: 2022.0100; 2023-504817-56 (Other Identifier: EMA CTIS NR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and metadata will be made available for reuse after removing data from participants who did not consent to reuse of their data and removing any potentially identifiable data. Data archiving and sharing will be done through DANS EASY. The Dublin Core metadata scheme will be used.
• IPD Sharing Time Frame: The data will only be made available for reuse after completion of the study and all planned publications of the results.
• IPD Sharing Access Criteria: Other researchers will be able to find the metadata in the data repository. They could express their interest in the dataset through emailing the PI. After meeting the sharing and reuse conditions and approval of the PI, data access will be provided through the data repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No