Evaluation of Oxygen Saturation Targets in Pediatric Respiratory Distress: A Randomized Controlled Trial on Bronchiolitis and Lower Respiratory Tract Infections

The primary objective of this study is to evaluate whether an **SpO2** threshold of 88% for children and adolescents admitted with respiratory distress, including conditions such as bronchiolitis, viral wheeze, and lower respiratory tract infection, results in a safe reduction in the length of hospital stay compared to an SpO2 threshold of 92%. This is clinically relevant as optimizing oxygen saturation targets could potentially reduce hospital resource utilization and improve patient outcomes.

Secondary objectives include investigating if an SpO2 threshold of 88% leads to differences in the duration and severity of symptoms, readmissions, time to normal activity, patient and parent quality of life, and cost-effectiveness compared to an SpO2 threshold of 92%. These factors are crucial for understanding the broader impact of oxygen saturation targets on patient recovery and healthcare costs.

The clinical trial involves a study population of children and adolescents aged 6 weeks to 12 years, both **male** and **female**, who are hospitalized with lower respiratory distress due to conditions such as **bronchiolitis**, viral wheeze, or lower respiratory tract infection. Participants require supplemental oxygen, indicated by an SpO2 level of less than 92% or as determined by the treating physician. The trial population was selected based on these specific medical conditions and the need for oxygen therapy. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, given the age range and health conditions of the participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of different oxygen saturation targets in children and adolescents with **respiratory distress**. This study is a **randomized controlled trial** with a double-blind design, ensuring that neither the participants nor the investigators are aware of the group assignments. The trial aims to compare the outcomes of maintaining an oxygen saturation (SpO2) threshold of 88% versus 92% in hospitalized patients. The primary objective is to determine if a lower SpO2 threshold can safely reduce the length of hospital stay. The trial is expected to run from July 2023 to December 2025.

Participants will be children aged 6 weeks to 12 years, admitted with conditions such as **bronchiolitis**, viral wheeze, or lower respiratory tract infection, and requiring supplemental oxygen. The study will include an initial screening visit to confirm eligibility based on the inclusion criteria, which include an SpO2 of less than 92% or as indicated by the treating physician. Following randomization, participants will undergo regular follow-up visits to monitor their health status, oxygen therapy duration, and any adverse events. The end-of-study visit will assess the primary endpoint, which is the time from admission to meeting all discharge criteria, along with secondary endpoints such as length of stay, number of PICU admissions, and overall pediatric health.

The expected duration of participant involvement is up to the point of discharge, with follow-up assessments conducted post-discharge to evaluate long-term outcomes such as quality of life and parental anxiety. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or any adverse events that compromise participant safety. The trial is categorized as a low-intervention study due to the use of **oxygen**, a medicinal gas with established market authorization, and the minimal additional risk posed by the follow-up procedures, which primarily consist of questionnaires.

The clinical trial involves the use of **Conoxia Liquid**, a medicinal gas in liquefied form, with a concentration of 100% v/v **oxygen**. This experimental medication is administered via the **respiratory route**. The product is manufactured by Linde Gas Therapeutics Benelux BV and is identified by the marketing authorization number RVG 112179. The **oxygen** used in this trial is of chemical origin, and the product is not formulated specifically for pediatric use. The maximum treatment period for the administration of this medicinal gas is limited to one day, with no specified maximum daily or total dose amount. The administration schedule and participant compliance are monitored to ensure adherence to the trial protocol.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial's primary objective is to evaluate the safety and efficacy of different oxygen saturation targets in children and adolescents with respiratory distress. The trial does not include any additional medicinal products or interventions beyond the administration of Conoxia Liquid. Compliance with the dosing schedule is critical, and participants' adherence is closely monitored throughout the trial duration to ensure the integrity of the study results.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the time from admission to meeting all discharge criteria, which will be used to determine the effectiveness of different **oxygen** saturation targets in reducing the length of hospital stay for children and adolescents with respiratory distress. Secondary endpoints include various parameters such as the length of stay, number of Pediatric Intensive Care Unit (PICU) admissions, time spent on oxygen therapy, duration of symptoms, time from admission to return to normal health, and time from admission to return to school or daycare. Additional secondary endpoints involve unscheduled healthcare visits after discharge during follow-up, patient quality of life, parental anxiety, overall pediatric health, economic evaluation, and reasons for starting oxygen therapy.

The trial will compare two **oxygen** saturation thresholds, 88% and 92%, to determine their impact on the aforementioned endpoints. The data collection will involve monitoring the patients' progress from admission through to discharge and beyond, using validated methods to ensure accuracy and reliability. The trial is designed to be a low-intervention study, with the use of **oxygen** as a medicinal gas within its authorized indications, and additional follow-up consisting only of questionnaires. This approach minimizes additional risk or burden to the participants compared to normal clinical practice.