Efficacy and Safety Comparison of Buckberg and Del Nido Cardioplegia in Isolated Myocardial Revascularization Surgery

The primary objective of this clinical trial is to evaluate the **efficacy** and **safety** of two cardioplegic solutions, Del Nido and Buckberg, in providing myocardial protection during isolated myocardial revascularization surgery with extracorporeal circulation. This is clinically relevant as it aims to determine which solution better minimizes myocardial injury, as measured by markers such as CK and Troponin T, and reduces in-hospital mortality, thereby potentially improving patient outcomes in cardiovascular surgery.

Secondary objectives include: - Comparing other markers of myocardial injury, such as perioperative myocardial infarction, left ventricular ejection fraction (LVEF) by transthoracic echocardiography, cardiac resonance, and the need for postoperative inotropes or ventricular assist devices. Additionally, the study will assess the spontaneous recovery of post-unclamping cardiac rhythm or the need for defibrillation. - Evaluating hemodilution parameters, including minimum intraoperative and postoperative hemoglobin levels and the need for transfusion, as well as intra and postoperative glucose and insulin requirements. Surgery times, such as total time, cardiopulmonary bypass (CPB) time, and aortic clamping time, along with other intraoperative and postoperative analytical parameters like maximum lactate, will also be compared. - Collecting data on adverse events in the postoperative period, including episodes of atrial fibrillation, renal failure and the need for replacement therapy, stroke, reintervention due to bleeding, and infection.

The clinical trial focuses on patients with **cardiovascular pathology** undergoing isolated myocardial revascularization surgery with extracorporeal circulation. The study population includes adults over the age of 18, encompassing both male and female participants. The trial does not involve a vulnerable population. Participants were selected based on their legal age, the specific surgical procedure they are undergoing, and their ability to provide informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria include being of legal age and undergoing the specified surgical procedure, while exclusion criteria are not detailed in the provided information.

The clinical trial is designed as a **randomized** and open-label study to evaluate the efficacy and safety of two cardioplegic solutions, Del Nido and Buckberg, in patients undergoing isolated myocardial revascularization surgery with extracorporeal circulation. The primary objective is to assess myocardial protection by comparing levels of myocardial injury markers, specifically CK and Troponin T, and in-hospital mortality between the two strategies. The trial is categorized as a Phase IV study with a low level of intervention, focusing on patients with **cardiovascular pathology**.

Participants will be involved in the study for an estimated duration from the recruitment start date on November 16, 2023, until the trial's estimated end date on July 1, 2027. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, type of surgery, and informed consent, followed by multiple follow-up visits to monitor postoperative outcomes. Daily measurements of myocardial damage markers will be conducted during the first five postoperative days, with peak levels typically occurring between days 2 and 4. The end-of-study visit will conclude the participant's involvement, assessing long-term outcomes such as left ventricular function and total hospitalization days.

Participants are expected to remain in the study for the entire duration unless specific conditions necessitate early termination. These conditions include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will also monitor secondary endpoints, including aortic clamping time, extracorporeal circulation time, and the need for postoperative interventions such as defibrillation or inotropes. The study aims to provide comprehensive data on the comparative effectiveness of the cardioplegic solutions, contributing valuable insights into myocardial protection strategies during cardiac surgery.

The clinical trial involves the use of an experimental medication known as **Cardioplegia Solutions**, which is a combination of four active substances: **calcium chloride**, **potassium chloride**, **sodium chloride**, and **magnesium chloride**. This medication is administered in a pharmaceutical form identified as PHF1195. The route of administration is intracoronary, specifically designed for use during myocardial revascularization surgery. The dosage is set at a maximum of 1 liter per day, with the total dose not exceeding 1 liter throughout the treatment period. The maximum treatment period is limited to one day. The solution is of chemical origin and is not formulated for pediatric use.

In addition to the experimental treatment, the study compares two cardioplegic solutions: Del Nido cardioplegia and Buckberg cardioplegia. These solutions are used as standard-of-care therapies in the context of myocardial protection during surgery. The trial aims to evaluate the efficacy and safety of these solutions by comparing levels of myocardial injury markers, such as CK and Troponin T, and assessing in-hospital mortality rates between the two strategies. Compliance with the dosing schedule and administration is monitored to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed by comparing two cardioplegic solutions, Del Nido and Buckberg, in patients undergoing isolated myocardial revascularization surgery with extracorporeal circulation. The primary endpoints for evaluating efficacy include the measurement of **myocardial injury markers**, specifically peak levels of CK (Creatine Kinase) in U/L and ultrasensitive Troponin T in ng/L. These markers will be determined daily during the first five postoperative days, with the peak levels typically occurring between postoperative days 2 and 4. Additionally, operative mortality will be assessed, defined as mortality within 30 days post-surgery or during the hospital admission if it exceeds 30 days.

Secondary endpoints include aortic clamping time, extracorporeal circulation time, spontaneous recovery of cardiac rhythm post-aortic unclamping, and the need for defibrillation or inotropes for weaning from cardiopulmonary bypass (CPB). Other parameters include maximum intraoperative blood glucose, insulin needs, hemoglobin levels, lactate levels, and the need for red blood cell transfusion. The trial will also monitor the need for mechanical circulatory assistance, perioperative myocardial infarction, episodes of de novo atrial fibrillation, intubation hours, left ventricular function at discharge, and cardiac resonance in a subgroup of patients. The duration of ICU and total hospitalization days will also be recorded. These efficacy parameters will be collected and analyzed to determine the comparative effectiveness of the cardioplegic solutions in providing myocardial protection.