Evaluation of Dexamethasone Phosphate on Complication Reduction and Mortality in Severe Burn Patients: A Randomized Controlled Trial

The primary objective of this study is to demonstrate the efficacy of **dexamethasone** in reducing major complications and all-cause mortality in patients with severe burns. This is clinically relevant as severe burns are associated with high morbidity and mortality rates, and effective interventions are crucial for improving patient outcomes.

Secondary objectives include:

• Demonstrating the efficacy of dexamethasone in reducing the rates of hospital-acquired infections, such as pneumonia and catheter-related bloodstream infections, and increasing antibiotic-free days.
• Assessing the efficacy of dexamethasone in decreasing respiratory complications and increasing ventilator-free days.
• Studying the impact of dexamethasone on ICU and hospital length-of-stay, as well as the risks of organ dysfunction.
• Evaluating the general tolerance of the treatment, focusing on hyperglycemia, hypernatremia, and hypokalaemia.
• Investigating the specific tolerance of the treatment on skin lesions, including surgical site infections and autograft failures.
• Examining the impact of treatment on serum CRP levels.
• Analyzing the impact of the timing of the first surgery on the main endpoint.

The clinical trial focuses on evaluating the efficacy of **dexamethasone** in patients with **severe burns**. The study population includes both male and female participants, aged between 18 and 80 years. Participants are required to have a total burn surface area of at least 20%, as assessed by a trained expert upon admission, and must be receiving invasive mechanical ventilation at the time of inclusion. The trial targets a vulnerable population, as it involves individuals within 48 hours of sustaining a burn injury. Participants must have informed and signed written consent from their next-of-kin or legal representative, or follow an emergency procedure in the absence of a legal representative. Additionally, participants must be affiliated with the French social security system or be beneficiaries of such a system. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **dexamethasone phosphate** in reducing major complications and mortality in patients with severe burns. This is a Phase III, randomized, double-blind, controlled trial. The trial will involve the administration of **dexamethasone phosphate** and a placebo, both delivered via intravenous use. The trial is expected to commence on June 1, 2025, and conclude by October 1, 2028. Participants will be involved in the study for a maximum treatment period of 5 days, with the total trial duration extending to 90 days for follow-up assessments.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 to 80 years), total burn surface area (≥ 20%), and the requirement for invasive mechanical ventilation within 48 hours of the burn injury. Informed consent must be obtained from the next-of-kin or legal representative. Follow-up visits will occur at specified intervals to monitor primary and secondary endpoints, including major complications like moderate to severe ARDS and AKI, as well as all-cause mortality at day 90. Secondary endpoints will assess hospital-acquired infections, respiratory complications, ICU and hospital length of stay, and general and specific tolerance within 28 days.

The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by participants. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with study procedures, or withdraw consent. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **DEXAMETHASONE PHOSPHATE**, a chemical compound used as the experimental medication. It is provided in the form of a solution for injection or infusion. The active substance, dexamethasone phosphate, is administered intravenously. The maximum daily dose is 20 mg, with a total maximum dose of 100 mg over a treatment period of up to 5 days. The primary objective of the trial is to evaluate the efficacy of dexamethasone in reducing major complications and mortality in patients with severe burns.

**SODIUM CHLORIDE** is utilized as a non-experimental treatment in this study, serving as a placebo. It is also provided as a solution for injection and is administered intravenously. The maximum daily dose is 1 DF dosage form, with a total maximum dose of 5 DF dosage forms over a treatment period of up to 5 days. Sodium chloride is used to maintain blinding in the trial and ensure that the administration procedures are consistent across all study participants.

The efficacy of dexamethasone in reducing major complications and all-cause mortality in patients with severe burns will be assessed through a series of hierarchical and secondary endpoints. The primary endpoints include the evaluation of major complications, specifically moderate to severe **Acute Respiratory Distress Syndrome (ARDS)** and Acute Kidney Injury (AKI) stages 2 to 3, within 28 days, as well as all-cause mortality at day 90. These endpoints will be tested sequentially for superiority, beginning with major complications. If superiority is demonstrated, the trial will proceed to test for superiority in reducing all-cause mortality.

Secondary endpoints encompass a range of clinical outcomes, including hospital-acquired infections such as pneumonia and catheter-related bloodstream infections within 28 days, respiratory complications like ARDS on day 28, and the number of invasive ventilator-free days by day 28. Additional measures include ICU and hospital length of stay, Sequential Organ Failure Assessment (SOFA) scores on days 1, 3, 7, and 14, and AKI stages 2 and 3 within 28 days. Tolerance will be assessed through the incidence of hyperglycemia, hypernatremia, hypokalemia, gastrointestinal bleeding, and acquired weakness within 28 days. Specific tolerance measures include surgical site infections and autograft failures, confirmed by an independent adjudication committee. Serum C-reactive protein (CRP) levels will be measured on days 0, 1, 3, 7, and 14, and the timing of the first surgery will also be recorded.