Evaluation of Epinephrine, Norepinephrine, and Phenylephrine on Intraoperative Hemodynamic Performance in Patients Undergoing Open Major Abdominal Surgery

The primary objective of this clinical trial is to evaluate the **time-weighted average (TWA)** of cardiac output during continuous infusion of **epinephrine**, **norepinephrine**, and **phenylephrine** in patients undergoing open major abdominal surgery. This objective is clinically relevant as it aims to determine the hemodynamic performance of these vasopressors, which are critical in managing intraoperative hemodynamics and ensuring adequate tissue perfusion during major surgical procedures.

Secondary objectives include assessing the TWA of intraoperative brain regional oxygen saturation (**brSO2**) and tissue regional oxygen saturation (**trSO2**) between the groups. These outcomes are important for understanding the effects of the vasopressors on cerebral and peripheral tissue oxygenation, which are vital parameters for patient safety and recovery during and after surgery.

The clinical trial involves **patients undergoing open major abdominal surgery**. The study population includes both male and female participants aged 45 years and older. Participants are required to be scheduled for moderate- to high-risk major open abdominal surgery expected to last at least two hours, with an ASA physical status of 2 or higher. The trial does not include a vulnerable population. Participants may have one or more risk factors such as advanced age, history of peripheral arterial disease, coronary artery disease, stroke, transient ischemic attack, chronic kidney disease, diabetes requiring medical treatment, current or significant history of smoking, heart failure, or elevated preoperative biomarkers like high-sensitivity Troponin T or NT-proBNP. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that the study population is representative of individuals who are at increased risk during major abdominal surgery, allowing for a comprehensive assessment of the trial's main objective concerning cardiac output management.

The clinical trial is designed to evaluate the effect of **epinephrine**, **norepinephrine**, and **phenylephrine** on intraoperative hemodynamic performance in patients undergoing open major abdominal surgery. This is a prospective, double-blind, randomized controlled trial. The primary objective is to assess the time-weighted average (TWA) of cardiac output during continuous infusion of the three drugs. Secondary endpoints include the TWA of brain regional oxygen saturation (brSO2) and tissue regional oxygen saturation (trSO2) values between the groups. The trial is categorized as a low-intervention Phase IV trial, as all medications are approved for intraoperative blood pressure management.

The trial is expected to run from September 18, 2022, to December 31, 2025. Participants will be involved for the duration of their surgery, with the maximum treatment period being one day. The inclusion criteria require participants to be 45 years or older, scheduled for moderate- to high-risk major open abdominal surgery lasting at least two hours, and having an ASA physical status of 2 or higher. Additionally, participants must have at least one specified risk factor, such as a history of coronary artery disease or chronic kidney disease. There are no specified exclusion criteria.

Study visits will follow a structured sequence. The initial visit will be a screening to confirm eligibility based on the inclusion criteria. During the surgery, participants will receive one of the three drugs via intravenous infusion, and their cardiac output and oxygen saturation levels will be monitored. Follow-up visits are not specified, as the trial focuses on intraoperative outcomes. The end-of-study visit will occur at the conclusion of the surgery, where final assessments will be made. Participants may be terminated early from the study if they do not meet the inclusion criteria or if any adverse events occur that compromise their safety.

The clinical trial involves the administration of three **experimental medications** to evaluate their effects on intraoperative hemodynamic performance. The first medication is **Biorphen 10 mg/ml Injektionslösung**, which contains the active substance **phenylephrine hydrochloride**. This medication is provided as a **solution for injection** and is administered via **intravenous infusion**. The maximum daily dose is 100 mg, with a total treatment period of one day. Phenylephrine acts as a **vasopressor**, and its chemical origin is confirmed. The product is manufactured by SINTETICA GMBH and is not a pediatric formulation.

The second medication is **Suprarenin 1mg/ml Ampullen**, containing **epinephrine hydrochloride** as the active ingredient. This medication is also a **solution for injection** and is administered through **intravenous infusion**. The maximum daily dose is 10 mg, with a treatment period limited to one day. Epinephrine functions as a **catecholamine** and is of chemical origin. The manufacturer of this product is CHEPLAPHARM ARZNEIMITTEL GMBH, and it is not formulated for pediatric use.

The third medication used in the trial is **Noradrenalin Kabi 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung**, which contains **noradrenaline tartrate**. This product is a **solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose is 10 mg, with a treatment period of one day. Noradrenaline is classified as a **catecholamine** and is chemically derived. The product is produced by FRESENIUS KABI AUSTRIA GMBH and is not intended for pediatric patients.

All medications are administered under controlled conditions, with compliance monitored throughout the trial. The study is designed to compare the time-weighted average of cardiac output between the continuous infusion of these medications. No non-experimental treatments, such as standard-of-care therapy or placebo, are utilized in this trial. The trial is conducted in a double-blinded, randomized manner to ensure the integrity of the results.

The efficacy of the clinical trial titled "The effect of epinephrine, norepinephrine and phenylephrine on intraoperative hemodynamic performance – a prospective double-blinded randomized clinical trial" will be assessed using specific primary and secondary endpoints. The primary endpoint is the **Time Weighted Average (TWA)** of cardiac output during continuous infusion of the three drugs: epinephrine, norepinephrine, and phenylephrine. This parameter will be measured to evaluate the hemodynamic performance of each drug during surgery.

Secondary endpoints include the TWA of intraoperative brain regional oxygen saturation (brSO2) and tissue regional oxygen saturation (trSO2) values between the groups. These secondary outcomes will provide additional insights into the effects of the drugs on oxygen saturation in different regions of the body during the surgical procedure.

The trial is designed as a low intervention study, as all medications involved are approved for intraoperative blood pressure management. The trial is categorized as a Phase IV trial, focusing on the post-marketing surveillance of the drugs' efficacy and safety in a real-world setting. The study is expected to conclude by December 31, 2025, with recruitment having started on September 18, 2022.