Corticosteroids Before Extubation in Pediatric Intensive Care Unit (COBEX-PED)

Corticoïdes Avant Extubation en réanimation pédiatrique : étude Multicentrique, Prospective, randomisée, Contre Placebo

Fifty to 60% of children admitted to a pediatric intensive care unit (PICU) are placed under invasive mechanical ventilation (MV) at least once during their stay. After extubation, about 30% of these patients will experience respiratory distress due to upper airway obstruction (RDUAO), and about one-third of these cases will require re-intubation. Treating this RDUAO extends the length of stay in the PICU.

Pre-extubation corticosteroid therapy has been validated in adults as a preventive treatment for the occurrence of RDUAO. However, the lack of robust data in pediatrics has not allowed for a consensus on the benefit of its use in children on MV in the PICU.

The investigators propose to conduct a randomized, multicenter, double-blind, placebo-controlled study evaluating the effect of intravenous dexamethasone (IV-DXM) before extubation on the incidence of RDUAO in children.

Study Overview

• Status: Not yet recruiting
• Conditions: Intensive Care Pediatric
• Intervention / Treatment: Drug: Dexamethasone IV; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 348
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Phone Number: +33 142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Stéphane Dauger, MD PhD; Phone Number: +33 140032187; Email: stephane.dauger@aphp.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients intubated with an endotracheal tube with or without a cuff,
• Aged from 2 days post-term to 6 years,
• On mechanical ventilation for at least 36 hours,

And meeting the following extubation criteria:

• Extubation planned by the medical team
• Fraction of inspired oxygen (FiO2) ≤ 45%,
• Oxygen saturation measured by pulse oximeter ≥ 95% or appropriate according to the pathology,
• Positive end-expiratory pressure (PEEP) ≤ 8 cmH2O,
• Peak inspiratory pressure ≤ 22 cmH2O or presence of cough.
• Affiliated with a social security system,
• Collection of informed consent from the parental authority, by both parents or the legal guardian(s).

Exclusion Criteria:

• Refusal of consent by at least one parent or by the legal guardian(s),

• Patient with a contraindication to IV-DXM:

  • Uncontrolled local or general infection,
  • Active viral infections (hepatitis, herpes, chickenpox, shingles),
  • Live vaccines,
  • Severe coagulation disorders,
  • Ongoing gastrointestinal bleeding,
  • Known hypersensitivity to IV-DXM or one of its excipients.
• Patient participating in another interventional study involving human subjects or being in the exclusion period following a previous study involving human subjects, if applicable,
• Patient receiving State Medical Aid,
• Patient on long-term NIV,
• Known upper airway pathology (UAP) before intubation or at the time of extubation,
• History of UAP surgery within the month preceding inclusion,
• Any situation deemed incompatible with the child's participation in the trial at the discretion of the investigating physician,
• Decision to limit or stop therapeutic interventions.
• Premature patients aged less than 40 weeks of gestation
• Newborns aged less than 2 days after post-term birth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo: 0.9% NaCl solution, prepared in a syringe of 5 to 10 ml and administered intravenously to the patient over 10 minutes every 6 hours. The treatment duration ranges from 6 hours (minimum of two doses: H0, H6) to 18 hours (maximum of four doses: H0, H6, H12, H18).
Experimental: Intravenous dexamethasone	Drug: Dexamethasone IV; IV-DXM 4mg/ml, injectable solution. Dosage of 0.25 mg/kg (maximum 5 mg per dose), prepared in a syringe of 5 to 10 ml and administered intravenously to the patient over 10 minutes every 6 hours. The treatment duration ranges from 6 hours (minimum of two doses: H0, H6) to 18 hours (maximum of four doses: H0, H6, H12, H18).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of respiratory distress due to upper airway obstruction (RDUAO)	Within 48 hours post-extubation

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of reintubation due to RDUAO	Within 48 hours following a planned extubation
Odds ratios associated with the occurrence of RDUAO	Within 48 hours post-extubation
Number of days of hospitalization in pediatric intensive care unit (PICU)	Up to 28 days
Number of ventilator-free days in PICU	Up to 28 days
Number of days with non-invasive ventilation (NIV) post-extubation	Up to 28 days
Incidence of IV-DXM side effects	Up to 48 hours post-extubation

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Corticosteroids; Intensive Care Pediatrics
• Additional Relevant MeSH Terms: Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: APHP220674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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