Evaluation of Intravenous L-Glutamic Acid for Prevention of Acute Kidney Injury Post-Coronary Artery Bypass Grafting in Non-Diabetic High-Risk Patients

The primary objective of this study is to establish the efficacy of intravenous **glutamate** infusion in preventing **acute kidney injury** (AKI) following coronary artery bypass surgery (CABG) in high-risk patients without diabetes. This is clinically relevant as AKI is a common and serious complication post-CABG, which can lead to increased morbidity and mortality. By potentially reducing the incidence of AKI, the study aims to improve postoperative outcomes and patient recovery.

Secondary objectives include evaluating the efficacy of intravenous glutamate infusion in mitigating the postoperative increase of NT-proBNP, a biomarker associated with heart failure, after coronary artery bypass surgery among high-risk patients without diabetes. This could provide insights into the broader cardiovascular protective effects of glutamate infusion in this patient population.

The clinical trial focuses on evaluating the efficacy of intravenous glutamate infusion in preventing **acute kidney injury** after coronary artery bypass surgery among high-risk patients without diabetes. The study population includes both male and female adult patients, specifically those who have undergone surgery on a heart-lung machine with coronary artery bypass grafting of at least two vessel disease or left main stenosis, with or without a concomitant procedure. Participants are selected based on specific criteria, including a EuroSCORE II of 3.0 or higher, with at least one cardiac or procedure-related risk factor, or a Left Ventricular Ejection Fraction of 0.30 or less, regardless of EuroSCORE II. The age range of participants falls within categories 3 and 4, indicating a focus on middle-aged to older adults. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants involved in the study.

The clinical trial is designed to evaluate the efficacy of **L-glutamic acid** infusion in preventing acute kidney injury (AKI) following coronary artery bypass surgery (CABG) in high-risk patients without diabetes. This is a randomized, double-blind, controlled trial, with a placebo group receiving 0.9% **sodium chloride** solution for intravenous infusion. The trial is expected to commence recruitment on March 1, 2025, and conclude by June 1, 2027. The study will involve adult patients who meet specific inclusion criteria, such as undergoing CABG with at least two-vessel disease or left main stenosis, and having a EuroSCORE II ≥ 3.0 or a Left Ventricular Ejection Fraction ≤ 0.30.

Participants will be involved in the study for a maximum treatment period of one day. The trial will include several key visits: an initial screening visit to assess eligibility, followed by the administration of the investigational product or placebo during the surgical procedure. Postoperative follow-up visits will be conducted to monitor the incidence of AKI, defined as a ≥ 50% increase in postoperative p-creatinine compared to preoperative values, and to measure secondary endpoints such as the increase in p-NT-proBNP levels from the day before surgery to the third postoperative day. The end-of-study visit will occur after the final follow-up assessments are completed.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, if they withdraw consent, or if they fail to comply with the study protocol. The trial aims to provide valuable insights into the potential benefits of L-glutamic acid infusion in reducing the risk of AKI in a specific patient population undergoing cardiac surgery.

The clinical trial involves the administration of **Sodium Chloride** as a **placebo** treatment. The pharmaceutical form of this medication is a **solution for infusion**, specifically a 0.9% Sodium Chloride solution intended for **intravenous** administration. The maximum daily dose is 500 ml, with the same amount being the total dose allowed per treatment period. The treatment is administered once daily for a maximum period of one day. The solution is chemically derived and is not a pediatric formulation. Compliance with the administration schedule is monitored to ensure adherence to the protocol.

The experimental treatment in this trial is **L-Glutamic Acid**, which is administered as a **solution for infusion**. This solution is prepared at a concentration of 0.125M and is intended for **intravenous infusion**. The maximum daily dose is 9 grams, with the total dose also capped at 9 grams per treatment period. The treatment is administered once daily for a maximum period of one day. The L-Glutamic Acid solution is chemically derived and is not formulated for pediatric use. Participant compliance with the dosing schedule is closely monitored to ensure the integrity of the trial data.

The efficacy of the clinical trial titled "Glutamate infusion for prevention of Acute Kidney Injury in surgery for ischemic heart disease: (GLUTAMICS III = GLUTAmate for Metabolic Intervention in Coronary Surgery III)" will be assessed through specific primary and secondary endpoints. The primary endpoint is the incidence of postoperative **acute kidney injury (AKI)**, which will be measured by a postoperative increase of 50% or more in p-creatinine levels compared to preoperative values. This parameter will provide a direct measure of kidney function following coronary artery bypass surgery (CABG) in high-risk patients without diabetes.

Secondary efficacy assessment will focus on the postoperative increase of p-NT-proBNP levels, measured from the day before surgery to the third postoperative day. This biomarker is indicative of cardiac stress and will help evaluate the broader cardiovascular impact of the intervention. The trial will utilize these endpoints to determine the effectiveness of intravenous glutamate infusion in preventing AKI and potentially improving cardiac outcomes in the specified patient population.