Evaluation of Levocarnitine and Cobamamide as Adjunctive Therapy in Septic Shock with Acute Kidney Injury: A Multicenter, Randomized, Controlled Trial

The primary objective of this study is to compare the 28-day **mortality** rates between patients with septic shock and acute renal insufficiency treated with **L-Carnitine** as an adjunct therapy versus those not receiving L-Carnitine adjunct therapy. This comparison is clinically relevant as it aims to determine the potential survival benefit of L-Carnitine in this critically ill population, which could influence treatment protocols for septic shock patients with renal complications.

Secondary objectives include:

• Comparing 10-day mortality rates of septic shock patients with renal insufficiency treated with L-Carnitine for 56 days versus those not receiving the adjunct therapy.
• Evaluating patient safety across study arms.
• Assessing further clinical outcomes, with a focus on nephrological outcomes.
• Studying and comparing the kinetic curves of free and total serum carnitine, as renal replacement therapy can rapidly deplete carnitine levels, which is crucial for interpreting study results.
• Establishing a bio-bank for future ancillary studies, such as kidney injury marker studies and investigations into carnitine responders versus non-responders.

The clinical trial focuses on patients diagnosed with **septic shock** and acute renal insufficiency. The study population includes both male and female participants, aged 18 years and older, who are admitted to an intensive care unit for sepsis or septic shock and present with acute renal failure necessitating extra-renal purification. The trial involves a vulnerable population, as it includes individuals with critical health conditions. Participants must have a KDIGO score of 3 and have initiated or are about to initiate renal replacement therapy within a specified timeframe. The sponsor has not provided the total number of participants involved in the study. The selection criteria ensure that participants are insured or beneficiaries of a health insurance plan, and the emergency inclusion procedure complies with French law. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, two-parallel group, superiority study to evaluate the efficacy of **L-carnitine** as an adjunct treatment for patients with septic shock and acute kidney injury. The trial will compare the 28-day mortality rates between patients receiving L-carnitine adjunct therapy and those who do not. The study is expected to run from March 2018 to May 2026, with the primary endpoint being mortality. Secondary endpoints include survival, days alive and not on renal replacement therapy, and days alive and free of organ failure, among others.

Participants will be involved in the study for a maximum treatment period of 10 days, with the administration of L-carnitine or placebo via **intravenous use**. The trial will include an initial screening visit to confirm eligibility based on criteria such as age, insurance status, and the presence of septic shock with acute renal insufficiency. Follow-up visits will be scheduled to monitor the patient's condition and collect data on the primary and secondary endpoints. The end-of-study visit will assess the overall outcomes and any adverse events experienced by the participants.

Inclusion criteria require participants to be at least 18 years old, admitted to an intensive care unit for sepsis or septic shock, and presenting with acute renal failure requiring renal replacement therapy. Exclusion criteria are not specified in the provided data. Participants may be terminated early from the study if they withdraw consent, experience adverse events, or if the investigator deems it necessary for their safety. The trial is not classified as a low-intervention study and is conducted under the guidelines of a multicenter, randomized, two-group, parallel superiority design.

The clinical trial involves the administration of **Sodium Chloride** as a **solution for injection**. This experimental medication is administered via the **intravenous route**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 50 mg/kg. The total dose over the treatment period is also capped at 50 mg/kg. The treatment duration is limited to a maximum of 10 days. Sodium Chloride is utilized in this study as a standard-of-care therapy, serving as a control to compare the effects of the experimental treatment.

The experimental treatment in this trial is **Levocarnitine**, which is administered as a **solution for injection or infusion**. The active substances in this formulation include **Cobamamide** and **Levocarnitine**. The administration route is intravenous, similar to the control treatment. The dosage for Levocarnitine is also determined by the participant's body weight, with a maximum daily dose of 50 mg/kg and a total dose limit of 50 mg/kg over the treatment period. The maximum treatment duration is 10 days. Levocarnitine is being evaluated as an adjunct therapy for patients with septic shock and acute kidney injury, with the primary objective of assessing its impact on 28-day mortality rates.

Efficacy in this clinical trial will be assessed primarily by comparing the 28-day mortality rates between patients with septic shock and acute kidney injury treated with **L-Carnitine** as an adjunct therapy and those not receiving this adjunct therapy. The primary endpoint is mortality. Secondary endpoints include survival, verified through vital status and death certificates, and various measures of days alive without specific medical interventions or conditions. These include days alive and not on renal replacement therapy, days alive and free of renal failure, days alive and free of organ failure, days alive and not on mechanical ventilation, days alive and not in the intensive care unit, days alive and not in the hospital, and days alive and free of catecholamines. The collection and analysis of these endpoints will be conducted throughout the trial duration, with specific timepoints for data collection not explicitly detailed. The trial is designed as a multicenter, randomized, two-parallel group, superiority study, ensuring a robust comparison between the treatment and control groups.