A Randomized Controlled Trial Comparing Sodium Chloride and Sodium Lactate in the Management of Severe Diabetic Ketoacidosis in ICU Patients

The primary objective of this study is to compare the efficacy of fluid resuscitation using **Ringer Lactate** versus isotonic saline in the resolution of severe **diabetic ketoacidosis** at 24 hours post-admission to the Intensive Care Unit (ICU). This comparison is clinically relevant as it aims to determine the optimal fluid therapy for rapid resolution of this acute metabolic complication, potentially improving patient outcomes and reducing ICU stay duration.

The clinical trial focuses on patients diagnosed with **diabetic ketoacidosis**, specifically those with severe cases requiring intensive care. The study population includes both male and female participants, with an age range spanning from adolescents to adults. The trial involves a vulnerable population, as it includes individuals admitted to the emergency department or directly to the ICU. Participants were selected based on specific criteria, including a blood or capillary glucose level greater than 11 mmol/L, ketonemia or ketonuria, and a venous or arterial pH less than 7.30 or bicarbonate less than 15 mmol/L. Additionally, the volume of fluid administered before inclusion was less than 1 liter. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **Ringer lactate** compared to isotonic saline in the management of severe **diabetic ketoacidosis**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment allocations, thus minimizing bias. The trial is expected to commence on January 20, 2025, and conclude by February 28, 2027. The primary objective is to assess the resolution of diabetic ketoacidosis at 24 hours post-admission to the Intensive Care Unit (ICU).

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as admission to the emergency department or direct ICU admission, a diagnosis of severe diabetic ketoacidosis, and a fluid volume administered before inclusion of less than 1 liter. The primary endpoint is the resolution of ketoacidosis, defined by achieving specific biochemical criteria at 24 hours from ICU admission. Follow-up visits will monitor the participants' progress and ensure adherence to the study protocol. The end-of-study visit will occur once the primary endpoint is assessed, or if the participant meets criteria for early termination.

The expected duration of participant involvement is approximately 24 hours, with the possibility of early termination if the participant experiences adverse events or fails to adhere to the study protocol. The trial will utilize **sodium chloride** and **sodium lactate** as the investigational products, administered via infusion, with a maximum daily dose of 7 liters. The study is categorized as low-intervention, with minimal additional risk or burden compared to standard clinical practice. Participants will be closely monitored throughout the trial to ensure safety and data integrity.

The clinical trial involves the administration of **Sodium Chloride**, a chemical compound used as an **electrolyte** solution. The pharmaceutical form of this experimental medication is a **solution for injection**, specifically designed for **infusion**. The maximum daily dose is set at 7 liters, with the same amount being the maximum total dose permissible during the trial. The treatment period is limited to a maximum of 1 day. This solution is not formulated for pediatric use and is administered via infusion to manage severe diabetic ketoacidosis. The trial aims to evaluate the efficacy of isotonic saline in comparison to Ringer lactate in resolving diabetic ketoacidosis within 24 hours of admission to the Intensive Care Unit (ICU).

**Sodium Lactate** is also utilized in this study as an **infusion** solution, serving as a comparator treatment. Like Sodium Chloride, it is administered in a maximum daily dose of 7 liters, with a total dose not exceeding this amount over the course of the trial. The treatment duration is similarly restricted to 1 day. Sodium Lactate, known as Ringer lactate, is used to assess its effectiveness against isotonic saline in the context of fluid resuscitation for patients with severe diabetic ketoacidosis. Both solutions are administered via infusion, and neither is intended for pediatric use. The trial is conducted under a double-blind, randomized controlled design to ensure unbiased results.

The efficacy of the clinical trial comparing isotonic saline and Ringer lactate in the management of severe **diabetic ketoacidosis** will be assessed using specific primary endpoints. The primary endpoint is the resolution of ketoacidosis allowing discharge from the Intensive Care Unit (ICU). This is defined by the proportion of patients meeting the following criteria at 24 hours from ICU admission: capillary or blood glucose levels below 11 mmol/L, undetectable ketonemia or ketonuria, and venous or arterial pH greater than 7.35 or venous or arterial bicarbonate levels exceeding 20 mmol/L.