Evaluation of High-Dose Intravenous Ascorbic Acid on Mortality and Organ Dysfunction in Septic ARDS Patients: A Randomized Controlled Trial

The primary objective of the study is to evaluate the effect of high-dose intravenous **vitamin C** compared to placebo on a composite outcome of death or persistent organ dysfunction in patients with sepsis complicated by acute respiratory distress syndrome (ARDS). Persistent organ dysfunction is defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors, assessed at 28 days. This objective is clinically relevant as it aims to determine whether vitamin C can reduce mortality or the need for prolonged organ support in this critically ill population, potentially improving patient outcomes and reducing healthcare resource utilization.

The clinical trial involves a study population comprising **patients with sepsis complicated by Acute Respiratory Distress Syndrome (ARDS)**. The trial includes both male and female participants aged 18 years and older. Participants are admitted to the Intensive Care Unit (ICU) with a proven or suspected infection as the primary diagnosis and are currently receiving continuous intravenous infusion of vasopressors and high-flow oxygen therapy, including CPAP, NIV, or invasive ventilation. The trial population is selected based on specific inclusion criteria, such as the presence of ARDS characterized by acute onset, bilateral opacities on chest imaging, and specific oxygenation and ventilation parameters. Participants must have signed informed consent, or consent must be obtained from a representative if the patient is unable to provide it. The trial includes individuals affiliated with a social security system or universal health coverage and allows for the inclusion of patients under guardianship or curatorship, as well as those in emergency situations. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the effect of high-dose intravenous **vitamin C** compared to placebo on mortality or persistent organ dysfunction at 28 days in patients with sepsis complicated by **acute respiratory distress syndrome (ARDS)**. The trial will involve the administration of **ascorbic acid** and **sodium chloride** as a placebo, both delivered via intravenous infusion. The study is expected to span approximately four years, with an estimated recruitment start date of July 6, 2022, and an estimated end date of January 6, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), ICU admission with a proven or suspected infection, and current treatment with vasopressors and high-flow oxygen or mechanical ventilation. Following the screening, participants will be randomly assigned to receive either the investigational product or placebo. The trial includes regular follow-up visits to monitor the participants' health status and treatment response, with assessments focusing on the primary endpoint of death or persistent organ dysfunction at 28 days. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any adverse events are addressed.

The expected length of participant involvement is up to 28 days, with the possibility of early termination if the participant experiences significant adverse effects, withdraws consent, or if the investigator deems it necessary for the participant's safety. The trial's primary endpoint is the composite of death or persistent organ dysfunction, defined as continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors at 28 days. Secondary endpoints are not specified in the provided data. The trial aims to provide valuable insights into the potential benefits of high-dose intravenous vitamin C in reducing organ dysfunction and mortality in septic ARDS patients.

The clinical trial involves the administration of two treatments: **LAROSCORBINE** and **SODIUM CHLORIDE**. **LAROSCORBINE** is the experimental medication, containing the active substance **ascorbic acid**, also known as **vitamin C**. It is provided in the form of a **solution for injection/infusion** and is administered intravenously. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 200 mg/kg and a total maximum dose of 800 mg/kg over the treatment period. The treatment is administered for a maximum period of 4 days. The administration route includes both **IV injection** and **IV infusion**. The trial aims to evaluate the effect of high-dose intravenous vitamin C on mortality or persistent organ dysfunction in patients with septic acute respiratory distress syndrome (ARDS).

**SODIUM CHLORIDE** serves as the placebo in this trial. It is administered in the form of an **infusion** and is delivered intravenously. The maximum daily volume administered is 200 ml, with a total maximum volume of 800 ml over the treatment period, which also spans up to 4 days. The use of **SODIUM CHLORIDE** as a placebo allows for a controlled comparison against the experimental treatment, ensuring that any observed effects can be attributed to the active intervention. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the clinical trial titled "LOVIT-ARDS" will be assessed by evaluating the primary endpoint, which is a composite of death or persistent organ dysfunction at 28 days. Persistent organ dysfunction is defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors. This endpoint will be measured in patients with **Acute Respiratory Distress Syndrome (ARDS)** who are admitted to the Intensive Care Unit (ICU) with a proven or suspected infection as the main diagnosis.

The trial aims to compare the effect of high-dose intravenous vitamin C versus placebo on the specified composite endpoint. The assessment will be conducted at 28 days post-treatment initiation. The trial is designed as a multicenter, concealed-allocation, parallel-group, blinded, randomized controlled trial. The primary endpoint will be evaluated using standardized criteria to ensure consistency and reliability in the measurement of outcomes across different trial sites.