Evaluation of Landiolol Hydrochloride and Sodium Chloride in Reducing Postoperative Low-Cardiac Output Syndrome in Mitral Valve Surgery: A Randomized Controlled Trial

The primary objective of this study is to evaluate the effect of administering **landiolol** as a cardioplegia adjuvant to reduce the occurrence of postoperative low-cardiac output syndrome (LCOS) in patients undergoing mitral valve surgery. This is clinically relevant as LCOS is a significant complication that can lead to increased morbidity and mortality following cardiac surgery.

Secondary objectives include assessing the expected cardiac protective effects of landiolol in various parameters: - Prolonged (>48 h) infusion of catecholamines - Postoperative peak of cardiac biomarkers (Troponin I or T) - Left ventricular ejection fraction - Need for new admission to hospital for cardiac reasons - Quality of life - Mortality

The clinical trial focuses on individuals diagnosed with **low-cardiac output syndrome (LCOS)**, specifically targeting those undergoing elective mitral valve repair or replacement surgery. The study population includes both male and female participants, all of whom are over the age of 18. Participants are required to have preoperative evidence of specific cardiac measurements, such as a left ventricular end-systolic diameter greater than 40 mm, a left ventricular end-diastolic diameter greater than 60 mm, or a left ventricular ejection fraction below 60%. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. All participants must have signed informed consent to be included in the study. The selection criteria ensure that the study population is homogenous in terms of the medical condition and surgical procedure, allowing for a focused assessment of the trial's main objective.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy of **landiolol hydrochloride** as a cardioplegia adjuvant in reducing the incidence of postoperative **low-cardiac output syndrome (LCOS)** in patients undergoing elective mitral valve surgery. The trial will involve the administration of Landiobloc 300 mg powder for solution for infusion, compared against a placebo of 0.9% sodium chloride solution. The study is set to commence recruitment on August 31, 2024, and is expected to conclude by January 31, 2027.

Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the reduction in the occurrence of postoperative LCOS. The study will include several key visits: an initial **screening visit** to confirm eligibility based on criteria such as age over 18 years, specific preoperative cardiac measurements, and signed informed consent. Follow-up visits will monitor the need for prolonged catecholamine infusion, use of circulatory mechanical assist devices, and requirement for renal replacement therapy, among other secondary endpoints. The **end-of-study visit** will assess the overall outcomes and any adverse events experienced by the participants.

Participants may be withdrawn from the study if they experience significant adverse effects or if they no longer meet the inclusion criteria. The trial will adhere to rigorous scientific standards to ensure the validity and reliability of the results, contributing valuable data to the understanding of LCOS management in cardiac surgery. The study's design and procedures are structured to maintain the integrity of the double-blind methodology, ensuring unbiased assessment of the intervention's efficacy.

The clinical trial involves the administration of **Landiolol Hydrochloride**, marketed under the name "Landiobloc 300 mg polvere per soluzione per infusione." This experimental medication is an ultra-short acting beta-blocker provided in the form of a powder for solution for infusion. The pharmaceutical form is a **solution for infusion**, and it is administered via **intravenous infusion**. The dosage is calculated based on body weight, with a maximum daily dose of 0.3 mg/kg. The treatment period is limited to a maximum of one day. The administration of Landiolol Hydrochloride is intended to assess its effect as a cardioplegia adjuvant in reducing the occurrence of postoperative low-cardiac output syndrome in patients undergoing mitral valve surgery. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to the experimental treatment, the study utilizes a non-experimental treatment, "SODIO CLORURO 0,9% BAXTER Soluzione per infusione," which serves as a placebo comparator. This product is a 0.9% saline solution, also provided in the form of a **solution for infusion**. It is administered intravenously, with the same dosage and treatment period as the experimental medication, ensuring consistency in administration across the study. The use of this saline solution allows for a controlled comparison to evaluate the efficacy of Landiolol Hydrochloride. Compliance with the administration of the placebo will also be monitored to ensure the integrity of the trial results.

Efficacy in the clinical trial titled "The use of Landiolol in mitral valve surgery: a randomized, controlled, double-blind trial (LUNA)" will be assessed primarily by evaluating the reduction in the occurrence of postoperative **low-cardiac output syndrome**. This condition is defined by the need for prolonged catecholamine infusion beyond 48 hours after the initiation of the study drug, the requirement for circulatory mechanical assist devices in the postoperative period, or the necessity for renal replacement therapy during the intensive care unit stay. These parameters will be measured and collected according to the criteria outlined in a recent JAMA publication (Cholley 2017).

Secondary endpoints include the number of patients requiring prolonged catecholamine infusion, increased postoperative cardiac biomarkers such as Troponin I or T, reduction in left ventricular ejection fraction, and the number of patients readmitted to the hospital for cardiac reasons. Additionally, patient-reported outcomes will be assessed using the EQ-5D-5L questionnaire, and mortality rates will be recorded. The schedule for measuring these endpoints will be aligned with the clinical trial protocol, ensuring systematic data collection and analysis throughout the study duration.