Comparison of Hemodynamic Effects of Isobaric Levobupivacaine and Isobaric Bupivacaine with Fentanyl in Subarachnoid Anesthesia for Hip Fracture in Patients Aged 65+

The primary objective of this study is to compare the **hemodynamic** effects of isobaric levobupivacaine and isobaric bupivacaine, both in combination with fentanyl, in patients aged 65 years or older undergoing hip fracture surgery. This comparison will focus on parameters such as invasive systolic arterial pressure, invasive diastolic arterial pressure, invasive mean arterial pressure, arterial oxygen saturation, and heart rate. Understanding these effects is clinically relevant as it may influence the choice of anesthetic agents in this patient population, potentially improving perioperative safety and outcomes.

Secondary objectives include comparing the possible adverse events during surgery and 48 hours post-surgery between both groups. This evaluation is crucial for assessing the overall safety profile of the anesthetic agents used in the study.

The clinical trial involves participants who are **65 years or older** and have undergone **hip fracture** surgery. The study population includes both male and female subjects, with no specific vulnerable populations selected. Participants are required to have a physical status classified between I and IV according to the American Society of Anesthesiologists (ASA), and they must weigh more than 40 kg and be taller than 140 cm, with a body mass index (BMI) of less than 50 kg/m². The trial population was selected based on their eligibility for intradural anesthesia with levobupivacaine and fentanyl or bupivacaine and fentanyl, as determined in the pre-anesthetic visit. Participants may have cardiovascular, respiratory, renal, or endocrine-metabolic conditions. The sponsor has not provided information regarding the total number of participants. All participants have provided informed consent to participate in the study.

The clinical trial is designed to evaluate the **hemodynamic** safety of isobaric **levobupivacaine** compared to isobaric **bupivacaine** in patients aged 65 years or older undergoing hip fracture surgery. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment is being administered, thus minimizing bias. The trial is categorized as a low-intervention study and is expected to conclude by December 31, 2025, with recruitment having commenced on March 1, 2018.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, surgical history, and physical status according to the American Society of Anesthesiologists (ASA) classification. The primary objective is to compare the effects of the two anesthetic combinations on invasive systolic arterial pressure (PASI), invasive diastolic arterial pressure (PADI), invasive mean arterial pressure (PAMI), arterial oxygen saturation (SatO2), and heart rate (HR). Secondary endpoints include measurements of cardiac index (CI), peripheral vascular resistance (PVR), and other relevant physiological parameters.

Participants will be involved in the study for a maximum treatment period of one day, with follow-up visits scheduled to monitor for adverse events, particularly cardiovascular and respiratory events, up to 48 hours post-surgery. The end-of-study visit will assess the overall outcomes and any long-term effects. Conditions that may lead to early termination from the study include withdrawal of consent or the occurrence of significant adverse events that compromise participant safety.

The clinical trial involves the administration of **Levobupivacaine**, marketed as Levobupivacaína Normon 5 mg/ml solución inyectable y para perfusión EFG. This experimental medication is provided in the form of a **solution for injection/infusion**. The active substance, levobupivacaine, is of chemical origin and is administered via **intravenous injection or infusion**. The maximum daily dose is 150 mg, with a total dose not exceeding 150 mg over a treatment period of one day. The pharmaceutical product is manufactured by Laboratorios Normon, S.A., and is not formulated for pediatric use. Participant compliance with the dosing schedule will be monitored throughout the trial.

The comparator treatment in this study is Inibsacain, which contains **bupivacaine hydrochloride** and **epinephrine** as active substances. This medication is also a **solution for injection**, provided in a cartridge form. The administration route is via injection, with a maximum daily and total dose of 150 mg, similar to the experimental medication. The treatment period is limited to one day. Inibsacain is produced by Laboratorios Inibsa, S.A., and is not intended for pediatric use. The trial will ensure adherence to the dosing regimen and monitor participant compliance accordingly.

Both treatments are used in combination with fentanyl to assess their hemodynamic effects in patients aged 65 years or older undergoing hip fracture surgery. The primary objective is to compare the effects on invasive systolic arterial pressure, invasive diastolic arterial pressure, invasive mean arterial pressure, arterial oxygen saturation, and heart rate. The trial is designed to ensure rigorous monitoring and accurate data collection to evaluate the safety and efficacy of the treatments.

The efficacy of the clinical trial will be assessed by comparing the hemodynamic effects of isobaric **levobupivacaine** and isobaric bupivacaine, both in combination with fentanyl, in patients aged 65 years or older undergoing hip fracture surgery. The primary endpoints for evaluating efficacy include invasive systolic arterial pressure (PASI), invasive diastolic arterial pressure (PADI), invasive mean arterial pressure (PAMI), arterial oxygen saturation (SatO2) measured in percentage, heart rate (HR) measured in beats per minute (bpm), and partial oxygen saturation (SpO2%) measured in percentage.

Secondary endpoints will include cardiac index (CI), peripheral vascular resistance (PVR), partial arterial oxygen pressure (PaO2), and partial arterial carbon dioxide pressure (PaCO2) measured in mmHg, pH, arterial lactate (Lc) measured in mmol/L, and arterial hemoglobin (Hb) measured in g/dL. Additionally, adverse events during surgery and up to 48 hours post-surgery, including cardiovascular and respiratory events associated with the surgical and anesthetic techniques, will be monitored. These parameters will be measured using appropriate clinical instruments and methodologies at specified timepoints throughout the trial to ensure accurate and reliable data collection for efficacy analysis.