Evaluation of Hypertonic Sodium Lactate Infusion for Reducing Post-Anoxic Brain Injury in Comatose Survivors of Cardiac Arrest

The primary objective of the LATTE trial is to evaluate the efficacy of **hypertonic sodium lactate** infusion in decreasing brain injury in comatose survivors following cardiac arrest. This is clinically relevant as it addresses the critical need to improve neurological outcomes and reduce morbidity in patients experiencing post-anoxic brain injury, a common consequence of cardiac arrest.

Secondary objectives include further evaluation of the treatment's efficacy on various clinical outcomes:

• Neurological outcome
• Hospitalization time
• Mortality
• Need for vasopressors
• Incidence of epilepsy
• Neuronal damage
• Astroglial damage
• Myocardial damage
• Safety of the hypertonic sodium lactate treatment

These secondary objectives aim to provide a comprehensive assessment of the treatment's impact on both the immediate and long-term health of patients, thereby informing clinical practice and improving patient care strategies in the context of post-cardiac arrest syndrome.

The clinical trial involves participants who have experienced **post-anoxic brain injury**, **coma**, **cardiac arrest**, or **post-cardiac arrest syndrome**. The study population includes both male and female subjects, aged over 18 years, who are in a comatose state with a Glasgow Coma Scale score of less than 9. Participants must have sustained a return of spontaneous circulation for at least 20 minutes, with the time to return of spontaneous circulation exceeding 15 minutes. The trial population is considered vulnerable due to their medical condition. The sponsor has not provided information regarding the total number of participants. Selection criteria focus on individuals who have survived cardiac arrest and are in a comatose state, ensuring the study targets those most likely to benefit from the intervention being tested.

The clinical trial is designed to evaluate the efficacy of **hypertonic sodium lactate** infusion in reducing brain injury in comatose survivors following cardiac arrest. This is a Phase 4, randomized, double-blind, controlled trial. The trial will involve two groups: one receiving the test product, **SODIO LATTATO MONICO 2 mEq/ml**, and the other receiving a placebo, **Plasmalyte A Viaflo**. Both products are administered via **intravenous infusion**. The trial is expected to commence recruitment on September 2, 2024, and conclude by November 30, 2030.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, sustained return of spontaneous circulation for at least 20 minutes, and a comatose state with a Glasgow Coma Scale score of less than 9. Follow-up visits will be scheduled to monitor primary and secondary endpoints, including neuron-specific enolase plasmatic peak values at 48 hours post-resuscitation, cerebral performance category scores at 90 days, and various other clinical and biochemical parameters. The end-of-study visit will assess the overall outcomes and any adverse events experienced by participants.

The expected duration of participant involvement is up to 90 days, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants. The primary endpoint is the measurement of neuron-specific enolase levels, while secondary endpoints include assessments of cerebral performance, length of stay in the ICU and hospital, mortality rates, and the incidence of seizures and adverse events. The trial aims to provide valuable insights into the potential benefits of hypertonic sodium lactate in improving outcomes for patients with post-anoxic brain injury and post-cardiac arrest syndrome.

The clinical trial involves the administration of two distinct **solutions for infusion**. The first experimental medication is **Plasmalyte A Viaflo**, a solution for infusion manufactured by Baxter SA. This isotonic electrolyte solution contains active substances including **magnesium chloride hexahydrate**, **potassium chloride**, **sodium chloride**, **sodium acetate trihydrate**, and **sodium gluconate**. The solution is administered via **intravenous infusion**. The maximum daily dose is 510 ml, with a total treatment period of one day. The solution is not a pediatric formulation and is classified under the ATC code B05BB01, indicating its use as an electrolyte solution.

The second experimental medication is **SODIO LATTATO MONICO 2 mEq/ml**, a concentrated solution for infusion produced by Monico S.P.A. This chemical solution contains **sodium lactate** as its active substance. It is also administered through **intravenous infusion**. The maximum daily dose is 22 mmol/kg, with a total treatment period of one day. This solution is not formulated for pediatric use and falls under the ATC code B05XA, which categorizes it as an electrolyte solution. Both solutions are used in the trial to evaluate the efficacy of hypertonic sodium lactate infusion in reducing brain injury after cardiac arrest in comatose survivors.

The efficacy of the clinical trial titled "Hypertonic LActaTe afTer cardiac arrEst: the LATTE trial" will be assessed through a series of primary and secondary endpoints. The primary endpoint is the measurement of **Neuron Specific Enolase (NSE)** plasmatic peak values at 48 hours after the return of spontaneous circulation. This biomarker is used to evaluate brain injury in comatose survivors following cardiac arrest.

Secondary endpoints include a variety of clinical and laboratory measures: the cerebral performance category score at 90 days, length of stay in the ICU and hospital, mortality rates during ICU and hospital stays, and at 90 days. Additional secondary endpoints involve the vasopressor equivalent dose during the first 48 hours post-resuscitation, seizure episodes within the first 24 and 48 hours, and during the ICU stay. Biomarker assessments will also be conducted, including peak plasmatic concentrations of neurofilament light chain (NFL), glial fibrillary acid protein (GFAP), and Troponin I (TnI) at 24, 48, and 72 hours. The incidence, nature, and severity of adverse events will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events.