Investigation of Initial Glucose Distribution Volume in Adults with Severe Burns Using Glucose 30% Injectable Solution

The primary objective of this study is to describe the mean values of the **initial distribution volume of glucose (IDVG)** during the first four days of management in patients with severe burns. This is clinically relevant as understanding the IDVG can provide insights into the fluid management and metabolic needs of severely burned patients, potentially improving outcomes and guiding therapeutic interventions.

Secondary objectives include:

• Correlation between IDVG, intra-thoracic blood volume (ITBV), and extra-vascular lung water (EVLW).
• Correlation between IDVG and body surface area (BSA).
• Correlation between IDVG and water intake and input/output balance.
• Correlation between IDVG at 24 to 48 hours and mortality.
• Description of glycemic changes before and after injection of the glucose bolus for IDVG measurement.

The clinical trial focuses on patients with **severe burns**, specifically those over 18 years of age who have sustained burns covering at least 30% of their body surface area due to a thermal mechanism. Both male and female participants are included, and the study population is considered vulnerable. Participants are required to be hospitalized at the CHR Metz-Thionville burn center and managed within 8 hours post-burn. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must be affiliated with a social security scheme, and written consent is necessary, either from the patient or a trusted person if the patient is unable to provide consent. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include the age and extent of burns, while exclusion criteria are not detailed in the available data.

The clinical trial is designed to evaluate the **initial distribution volume of glucose (IDVG)** in adults with severe burns. This is a Phase IV, randomized, double-blind, controlled study. The trial aims to describe the mean values of IDVG during the first four days of management in severely burned patients. The study will commence recruitment on September 1, 2024, and is estimated to conclude by January 1, 2027. Participants will be involved in the study for a maximum of four days, with the primary endpoint being the calculation of IDVG using a method described by Hitota et al. Secondary endpoints include measurements of intra-thoracic blood volume (ITBV) and extra-vascular lung water (EVLW), body surface area assessment, water intake and output balance, in-hospital mortality, and arterial blood glucose levels.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age over 18, hospitalization with burns covering at least 30% of body surface area, and management within eight hours post-burn. Written consent is required, either from the patient or a trusted person if the patient is unable to provide consent. Follow-up visits will occur daily for four days, during which glucose distribution and other physiological parameters will be monitored. The end-of-study visit will coincide with the final follow-up visit on the fourth day. Participants may be terminated early from the study if they withdraw consent, experience adverse events, or if the investigator deems it necessary for safety reasons.

The clinical trial involves the administration of **GLUCOSE 30% PROAMP**, a **solution for injection**. This experimental medication is formulated as a **solution injectable** and is intended for intravenous administration, either through **IV injection** or **IV infusion**. The active substance in this formulation is **glucose**, which is of chemical origin. The maximum daily dose is set at 300 mg/kg/h, with the same limit for the total dose amount. The treatment period is restricted to a maximum of four days. The product is manufactured by **Laboratoire Aguettant** and is not a pediatric formulation. The trial aims to evaluate the initial distribution volume of glucose in severely burned adults over the first four days of management.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The focus remains solely on the administration of the experimental glucose solution. Participant compliance with the dosing schedule will be monitored to ensure adherence to the specified administration guidelines. The trial does not involve any additional medicinal products or devices.

Efficacy in this clinical trial will be assessed primarily through the calculation of the initial distribution volume of **glucose** (IDVG) during the first four days of management in severely burned patients. The IDVG is determined using a method described by Hitota et al., which involves measuring a reference blood glucose level from an arterial blood sample using a blood glucose meter. Following this, a bolus of 5 g of glucose is injected into a central venous line over 30 seconds, and a second blood glucose level is measured 3 minutes post-injection. The difference between these two glucose levels, recorded as d[glu] in mg/dl, is used in the formula: IDVG = 24.4 x e(-0.0298 * d[glu]) + 2.7, to calculate the IDVG in liters.

Secondary endpoints include the measurement of intra-thoracic blood volume (ITBV) and extra-vascular lung water (EVLW) at the same time as IDVG, utilizing the PiCCO device and trans-lung dilution of a thermal indicator (cold saline). Additional secondary endpoints are the assessment of body surface area on admission using the Wallace method, water intake and input/output balance, and in-hospital mortality. Arterial blood glucose levels will also be measured in g/L just before and 3 minutes after the glucose bolus injection, using a glucometer. These measurements will provide comprehensive data on the efficacy of the treatment protocol in managing glucose distribution and related physiological parameters in the study population.