Evaluation of Goal-Directed Hemodynamic Therapy Using Starling™ SV System on Postoperative Complications in Elective Neurosurgery with Isolyte and Gelaspan Infusions

The primary objective of this clinical trial is to determine the effect of **goal-directed hemodynamic therapy** (GDHT) guided by the non-invasive Starling™ SV System on the incidence of postoperative complications in patients undergoing neurosurgical intervention. This is clinically relevant as it aims to optimize fluid management during surgery, potentially reducing complications and improving patient outcomes in elective neurosurgery for unspecified brain conditions.

Secondary objectives include:

• Investigating additional safety information to ensure the comprehensive assessment of the intervention's risk profile.
• Comparing hemodynamic characteristics and their changes over time between study groups to evaluate the physiological impact of the therapy.
• Comparing laboratory values of selected blood parameters and their changes over time between study groups to assess biochemical responses to the treatment.
• Comparing fluid balance and fluid therapy between study groups to understand the differences in fluid management strategies.

The clinical trial involves participants undergoing **elective neurosurgery** for unspecified brain conditions. The study population includes both male and female subjects aged 18 years and older. Participants are selected based on their eligibility for elective brain surgery with an expected duration of at least two hours and are classified within Category 1-3 according to the ASA Physical Status Classification. The trial includes individuals who are positioned laterally or supine during surgery and have provided informed consent. The sponsor has not provided the total number of participants. The trial population encompasses a vulnerable group, and lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, controlled study to evaluate the effects of goal-directed fluid management on postoperative complications in patients undergoing elective neurosurgery. The trial will utilize a non-invasive device, the Starling™ SV System, to guide fluid management. The study will involve two groups, with participants randomly assigned to either the intervention or control group. The trial is expected to commence recruitment on September 2, 2024, and conclude by December 2, 2027, with an estimated duration of three years.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility criteria are assessed. Key inclusion criteria include being 18 years or older, undergoing elective brain surgery expected to last at least two hours, and having a physical status classification of 1-3 according to the ASA. Participants must also provide informed consent. Exclusion criteria are not specified. Following the inclusion visit, participants will attend follow-up visits to monitor the incidence of adverse events and other secondary endpoints such as duration of surgery, length of stay in the ICU, and 28-day mortality. The end-of-study visit will evaluate the primary endpoint, which is the incidence of adverse events of special interest in both study groups.

The expected length of participant involvement is up to two days, corresponding to the maximum treatment period with the investigational products, which include Isolyte infuzní roztok and Gelaspan 4%, both administered as solutions for infusion. Participants may receive a maximum daily dose of 3 liters and a total dose of 6 liters. Conditions that may lead to early termination from the study include withdrawal of consent or the occurrence of significant adverse events. The trial aims to provide valuable insights into the management of fluid therapy in neurosurgical settings, potentially influencing future clinical practices.

The clinical trial involves the administration of two experimental medications, both in the form of a **solution for infusion**. The first medication, **Isolyte infuzní roztok**, is composed of **magnesium chloride hexahydrate**, **potassium chloride**, **sodium chloride**, and **sodium acetate trihydrate**. This solution is administered via **intravenous bolus injection/IV infusion**. The maximum daily dose is 3 liters, with a total maximum dose of 6 liters over a treatment period of up to 2 days. The solution is manufactured by Fresenius Kabi S.R.O. and is not a pediatric formulation.

The second medication, **Gelaspan 4%, infuzní roztok**, contains **magnesium chloride hexahydrate**, **potassium chloride**, **sodium chloride**, **calcium chloride dihydrate**, **sodium acetate trihydrate**, and **succinylated gelatin**. This solution is administered through **intravenous administration**. Similar to the first medication, the maximum daily dose is 3 liters, with a total maximum dose of 6 liters over a treatment period of up to 2 days. This solution is produced by B.Braun Melsungen AG and is also not formulated for pediatric use.

Both medications are used as part of a goal-directed fluid management strategy in the clinical trial, which aims to assess their impact on the incidence of postoperative complications in patients undergoing neurosurgical interventions. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by evaluating the impact of goal-directed hemodynamic therapy (GDHT) guided by the non-invasive Starling™ SV System on the incidence of postoperative complications in patients undergoing neurosurgical intervention. The primary endpoint for efficacy assessment is the incidence of adverse events and reactions, specifically focusing on Adverse Events of Special Interest (AESI) in both study groups.

Secondary endpoints include a range of parameters such as the duration of surgery, length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day mortality, and a descriptive analysis of any adverse events and reactions. Additional secondary endpoints involve monitoring mean arterial pressure (MAP), heart rate (HR), stroke volume variation (SVV), the number of episodes of hypotension, and the number of vasopressor administrations. Laboratory parameters such as hemoglobin and plasma lactate levels will also be measured. Furthermore, the volume of blood loss, urinary output, the number of administered units of packed red blood cells (RBC), and the consumption of crystalloid and colloid solutions will be recorded, along with the number of subjects receiving transfusions and the administration of crystalloid boluses.