Evaluation of Dexamethasone Phosphate for Reducing Respiratory Distress Post-Extubation in Pediatric Intensive Care: A Randomized, Double-Blind, Multicenter Study

The primary objective of this study is to evaluate the effectiveness of **DXM-IV** (dexamethasone phosphate) in reducing the incidence of **respiratory distress** due to upper airway obstruction in children hospitalized in the pediatric intensive care unit (URP) compared to a placebo. This is clinically relevant as it aims to improve patient outcomes by potentially decreasing the occurrence of respiratory complications following extubation, which is a critical concern in pediatric intensive care settings.

Secondary objectives include:

• Evaluation of the extubation failure rate.
• Identification of risk factors for post-extubation respiratory distress in children.
• Evaluate the effect of DXM-IV on the length of stay in URP.
• Evaluate the number of days free of ventilatory assistance in URP.
• Evaluation of the delay in weaning from non-invasive ventilation.
• Evaluation of the safety of DXM-IV in this indication with research into side effects.

The clinical trial involves a study population of children aged from 2 days post-term to 6 years, who are experiencing **respiratory distress** due to upper airway obstruction. The trial includes both male and female participants, and the population is considered vulnerable due to the young age of the subjects. Participants are required to be intubated with an intubation tube, with or without a cuff, and must be under mechanical ventilation for at least 36 hours. The trial population was selected based on specific extubation criteria, including planned extubation by the medical team, an inspired fraction of oxygen (FiO2) of 45% or less, oxygen saturation measured by pulse oximeter of 95% or more, positive expiratory pressure of 8 cmH2O or less, and peak inspiratory pressure of 22 cmH2O or less, or the presence of a cough. Participants must be affiliated with a social security system, and informed consent must be obtained from the parental authority, either by both parents or by the legal guardian(s). The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effectiveness of **dexamethasone phosphate** administered intravenously in reducing the incidence of **respiratory distress due to upper airway obstruction** in children hospitalized in a pediatric intensive care unit. This study is a prospective, randomized, double-blind, multicenter trial comparing the active treatment with a placebo. The trial is expected to commence recruitment on September 2, 2024, and conclude by September 3, 2027. Participants will be randomly assigned to receive either the active treatment or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study.

The trial will include several study visits, beginning with a screening visit to assess eligibility based on specific inclusion criteria, such as age between 2 days post-term to 6 years, intubation status, and extubation readiness. Following successful screening, participants will be enrolled and randomized. The primary endpoint is the cumulative incidence of **DRPE/OVAS** within 48 hours post-extubation, with secondary endpoints including reintubation rates, hospitalization duration, and side effects of the treatment. Follow-up visits will be conducted to monitor these outcomes, with the final visit marking the end of the study for each participant.

Participant involvement is expected to last until 48 hours post-extubation, with the possibility of early termination if criteria such as withdrawal of consent or adverse events are met. The trial's methodology ensures rigorous data collection and analysis to assess the efficacy and safety of the intervention, contributing valuable insights into the management of respiratory distress in pediatric patients.

The clinical trial involves the administration of **DEXAMETHASONE PHOSPHATE**, which is the experimental medication under investigation. This medication is provided in the form of a **solution for injection** and is administered via the **intravenous route**. The dosage is set at a maximum of 20 mg per day, with the total dose not exceeding 20 mg. The treatment period is limited to a single day. The active substance, **dexamethasone phosphate**, is of chemical origin. The trial aims to evaluate the effectiveness of this medication in reducing the incidence of dexamethasone-related post-extubation stridor or upper airway obstruction in children hospitalized in the pediatric intensive care unit.

In addition to the experimental medication, a **placebo** is utilized as a comparator treatment in this study. The placebo is designed to mimic the appearance and administration route of the dexamethasone phosphate solution, ensuring that the study remains double-blind. The placebo does not contain any active pharmaceutical ingredients and is administered intravenously, following the same schedule as the experimental treatment. This allows for a controlled comparison to assess the true efficacy of dexamethasone phosphate in the clinical setting.

The efficacy of the clinical trial titled "COBEX-PED Corticosteroids before extubation in pediatric intensive care unit: a prospective randomized double-blind multicenter study" will be assessed using both primary and secondary endpoints. The primary endpoint is the cumulative incidence of **DRPE/OVAS** (Dexamethasone-Related Post-Extubation/Obstructive Ventilatory Assistance Syndrome) within 48 hours post-extubation. Secondary endpoints include the cumulative incidence of reintubation due to **DRPE/OVAS** within 48 hours of planned extubation, odds ratios associated with the occurrence of **DRPE/OVAS** within 48 hours post-extubation, the number of days of hospitalization in the pediatric intensive care unit, the number of days free of ventilatory assistance, the number of days with non-invasive ventilation post-extubation, and the incidence of side effects of intravenous dexamethasone (DXM-IV) occurring from randomization to 48 hours post-extubation.