Evaluation of Hemodynamic and Hemostatic Effects of Intravenous Ringer's Lactate at 10°C and 22°C in Healthy Adults: A Randomized Crossover Study

The primary objective of this randomized controlled crossover study is to evaluate the effect of **Ringer's lactate** solution at different temperatures on the physiological response in healthy adults. Specifically, the study aims to compare the impact of Ringer's lactate at 10 degrees Celsius versus 22 degrees Celsius on **hemodynamic parameters**. This investigation is clinically relevant as it may provide insights into the optimal temperature for intravenous fluid administration, potentially influencing clinical practices in fluid resuscitation and management of patients requiring intravenous fluids.

The clinical trial involves a study population of **healthy adults** aged between 18 and 64 years. Both male and female participants are included, and the trial does not involve any vulnerable populations. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, focusing on individuals within the specified age range. Participants' general health status is considered healthy, and no specific lifestyle considerations such as diet or physical activity are highlighted. The study aims to investigate the effect of Ringer's lactate solution at varying temperatures on physiological responses, specifically examining **hemodynamic parameters**. The trial does not specify any significant exclusion criteria beyond the age range and health status.

This clinical trial is a **randomized controlled crossover study** designed to evaluate the effects of Ringer's lactate solution at varying temperatures on physiological responses in healthy adults. The trial will assess the impact of the solution, administered via **intravenous infusion**, on **hemodynamic parameters** by comparing cold fluids at 10 degrees Celsius to room temperature fluids at 22 degrees Celsius. The primary endpoint is the increase in mean arterial pressure (MAP) 30 minutes after the start of the infusion, measured using a standard non-invasive blood pressure cuff. Secondary endpoints include the time until MAP returns to baseline, changes in visual analog scale (VAS) during infusion, and various physiological and biochemical parameters at specified intervals.

The trial is expected to commence recruitment on October 2, 2023, and conclude by December 31, 2023. Participants will be involved in the study for a maximum of two days, with the possibility of early termination if they do not meet the inclusion criteria, which require participants to be aged between 18 and 64 years. The study visits will include an initial screening visit to confirm eligibility, followed by the administration of the investigational product on two separate occasions, allowing for the crossover design. Each administration will be followed by monitoring visits to assess the primary and secondary endpoints. The end-of-study visit will occur after the final monitoring session to ensure participant safety and collect final data.

Participants will receive a maximum daily dose of 1 liter and a total dose of 2 liters of the investigational product, Ringer-lactat Fresenius Kabi, which contains **potassium chloride, sodium chloride, calcium chloride dihydrate, and sodium lactate**. The trial is categorized as a Phase 3 therapeutic use clinical trial, with the investigational medicinal product having a marketing authorization and being used in accordance with the Summary of Product Characteristics (SmPC). The study is not classified as low intervention, and the investigational product is not a pediatric formulation or an orphan drug. The trial's design ensures rigorous control and blinding to maintain the integrity of the data collected.

The clinical trial involves the administration of **Ringer-lactat Fresenius Kabi**, a **solution for infusion**. This experimental medication is composed of the active substances **potassium chloride**, **sodium chloride**, **calcium chloride dihydrate**, and **sodium lactate** (as a 50% solution). The pharmaceutical form is a solution intended for intravenous infusion. The maximum daily dose is 1 liter, with a total maximum dose of 2 liters over the treatment period. The maximum treatment period is 2 days. The solution is administered via intravenous infusion, and the study investigates the effects of the solution at different temperatures (10 and 22 degrees Celsius) on circulation and hemostasis in healthy volunteers.

There are no non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, specified in this study. The trial is designed as a randomized controlled crossover study, focusing on the physiological response to the Ringer's lactate solution. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol. The study does not involve any pediatric formulations or orphan drug designations. The product is manufactured by Fresenius Kabi AB and is authorized for use in Denmark.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the increase in **mean arterial pressure (MAP)** 30 minutes after the initiation of the fluid bolus infusion, which will be measured using a standard non-invasive blood pressure cuff. Secondary endpoints include the time until MAP returns to baseline value post-infusion, changes in Visual Analogue Scale (VAS) scores during infusion, and variations in physiological parameters such as temperature, blood pressure, heart rate, peripheral oxygen saturation, cardiac index, cardiac output, total peripheral resistance index, and stroke volume. Additionally, changes in intravascular volume status and fluid responsiveness will be evaluated.

Biochemical parameters and ROTEM analysis will be assessed at baseline, 30 minutes, and 60 minutes post-infusion to further evaluate efficacy. These measurements will provide comprehensive data on the physiological response to the Ringer's lactate solution administered at different temperatures. The trial is designed as a randomized controlled crossover study, ensuring robust data collection and analysis. The schedule for these assessments is structured to capture both immediate and short-term physiological changes, providing a detailed understanding of the treatment's efficacy.