Evaluation of Norepinephrine Infusion Versus Standard Blood Pressure Management in Perioperative Hypotension During Non-Cardiac Surgery

The primary objective of this study is to evaluate whether perioperative **noradrenaline** infusion is superior to standard blood pressure management in reducing the occurrence of perioperative **hypotension** in patients undergoing non-cardiac surgery. This is clinically relevant as managing perioperative hypotension is crucial for minimizing complications and improving surgical outcomes in non-cardiac procedures.

The clinical trial focuses on patients undergoing non-cardiac surgery who are at risk of **hypotension**. The study population includes both male and female participants aged 45 years and older. Participants are required to be in good general health, classified as American Society of Anesthesiologists (ASA) physical status class II or higher. The trial does not involve a vulnerable population. Participants are selected based on their scheduled elective or accelerated non-cardiac surgery, which is expected to last at least one hour and requires general, neuraxial, or combined general and neuraxial anesthesia. Additionally, participants are expected to require at least an overnight hospital stay. 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.

The clinical trial is designed to evaluate the efficacy of **norepinephrine** infusion compared to standard blood pressure management in preventing perioperative hypotension in patients undergoing non-cardiac surgery. This is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence on July 1, 2024, and conclude by June 30, 2027, with the primary objective of assessing the occurrence of perioperative hypotension, defined as any mean arterial pressure (MAP) reading ≤55 mmHg during and up to 4 hours post-surgery.

Participants will be involved in the study for a period that includes preoperative screening, the surgical procedure, and postoperative follow-up. The inclusion visit will involve screening to ensure participants meet the criteria, such as being 45 years or older, undergoing elective or accelerated non-cardiac surgery lasting at least one hour, and requiring an overnight hospital stay. Written informed consent is mandatory, and participants must have an American Society of Anesthesiologists (ASA) physical status class II or higher. Follow-up visits will monitor secondary outcomes, including time under MAP ≤60 mmHg, major perfusion-related complications, and days alive and at home up to 30 days post-surgery. The end-of-study visit will assess the overall health status and any adverse events experienced by the participants.

The expected length of participant involvement is approximately 30 days post-surgery, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will utilize **LEVONOR**, a solution for infusion containing norepinephrine, with a maximum daily dose of 10 micrograms. The study aims to provide robust data on the effectiveness of norepinephrine in managing perioperative hypotension, potentially influencing future clinical practices in non-cardiac surgeries.

The clinical trial involves the administration of **norepinephrine**, marketed under the name LEVONOR, as the experimental medication. LEVONOR is a **solution for infusion** with a concentration of 1 mg/ml. The active substance, **norepinephrine**, also known as **noradrenaline** or **levarterenol**, is a chemical compound used primarily for its vasoconstrictive properties. The pharmaceutical form is a concentrate for solution for infusion, and it is administered intravenously. The maximum daily dose is 10 micrograms, with the same amount being the maximum total dose allowed per day. The treatment period is limited to one day. The product is manufactured by Zakłady Farmaceutyczne Polpharma S.A. in Poland and is not a pediatric formulation.

In addition to the experimental treatment, the study includes a comparator treatment, which is the standard blood pressure management protocol. This standard-of-care therapy serves as the control to evaluate the efficacy of the norepinephrine infusion in managing perioperative hypotension in patients undergoing noncardiac surgery. The standard blood pressure management protocol is not specified in detail within the provided data, but it typically involves the use of medications and interventions commonly accepted in clinical practice for maintaining blood pressure during surgery.

Participant compliance with the dosing schedule and administration of the experimental medication will be monitored throughout the trial. The study aims to assess whether the perioperative infusion of norepinephrine is superior to standard blood pressure management in reducing the incidence of perioperative hypotension. The trial is designed to ensure rigorous adherence to the dosing regimen and to evaluate the outcomes effectively.

Efficacy in the clinical trial will be assessed by evaluating the occurrence of perioperative **hypotension** in patients undergoing noncardiac surgery. The primary endpoint is defined as any mean arterial pressure (MAP) reading ≤55 mmHg during and up to 4 hours after surgery. Secondary endpoints include the duration of time under MAP ≤60 mmHg both intraoperatively and postoperatively, as well as a composite of major perfusion-related complications such as myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), stroke, non-fatal cardiac arrest, sepsis, and death from all causes. Additional secondary outcomes include infusion-related reactions and the number of days patients are alive and at home up to 30 days post-surgery.