Evaluation of Intrathecal Morphine and Bupivacaine Versus Intravenous Lidocaine on Postoperative Recovery in Robot-Assisted Upper Urologic Surgery

The primary objective of this study is to evaluate whether the addition of **spinal analgesia** with bupivacaine and morphine in patients undergoing robotic-assisted laparoscopic upper urinary tract surgery under general anesthesia enhances postoperative recovery. This is quantified using the patient-centered outcome scale "Quality of Recovery 15". The clinical relevance of this objective lies in potentially improving patient recovery experiences and outcomes following complex urological procedures, which can lead to better overall patient satisfaction and reduced healthcare costs.

Secondary objectives include assessing whether the addition of spinal analgesia with bupivacaine and morphine is associated with: - Reduced postoperative pain - Faster mobilization - Shorter hospital stay - Fewer complications Additionally, the study will analyze the effects on intraoperative hemodynamics and perioperative inflammatory markers. These secondary objectives aim to provide a comprehensive understanding of the benefits and potential risks associated with spinal analgesia in this surgical context.

The clinical trial involves participants diagnosed with **renal or ureter malignancy**, renal or ureter benign tumor, nephrolithiasis, or renal reflux. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The trial does not specifically target a vulnerable population. Participants were selected based on their scheduled elective robotic-assisted upper urinary tract surgery at one of the participating hospitals, and they provided oral and written informed consent after receiving comprehensive information about the study. The sponsor has not provided the total number of participants involved in the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, assessor-blind, multicenter study to evaluate the effects of intrathecal **morphine** or intravenous **lidocaine** on postoperative recovery following robotic-assisted upper urologic surgery. The trial aims to determine whether the addition of spinal analgesia with **bupivacaine** and morphine in patients undergoing robotic-assisted laparoscopic upper urinary tract surgery under general anesthesia improves recovery, as measured by the patient-centered outcome scale "Quality of Recovery 15" (QoR-15). The study will include patients scheduled for elective robotic-assisted upper urinary tract surgery who provide informed consent. The trial is expected to commence recruitment on September 1, 2023, and conclude by December 31, 2025.

Participants will be involved in the study for a maximum treatment period of one day. The trial will include several key visits: an initial screening visit to confirm eligibility, followed by the surgical procedure and subsequent postoperative assessments. The primary endpoint is the QoR-15 score on postoperative day 1, with secondary endpoints including preoperative QoR-15 scores, pain assessments using the Numeric Rating Scale (NRS) at various postoperative intervals, and other recovery-related metrics. Follow-up visits will occur on postoperative days 1 to 3, with additional assessments on day 7 and at the end of the study period. The end-of-study visit will evaluate long-term recovery outcomes and any postoperative complications up to 30 days post-surgery.

Participants may be withdrawn from the study if they experience adverse events that necessitate discontinuation of the investigational product, fail to comply with study procedures, or withdraw consent. The trial will utilize a controlled design, with participants randomly assigned to receive either the test or comparator product. The test products include intrathecal morphine and bupivacaine, while the comparator is intravenous lidocaine. The study will ensure blinding of assessors to minimize bias in outcome evaluation. The trial's rigorous methodology and comprehensive follow-up schedule are designed to provide robust data on the efficacy and safety of the interventions in enhancing postoperative recovery.

The clinical trial involves the administration of **morphine**, derived from an **extract of fresh opium poppy** with an extraction solvent of ethanol 31.2% (m/m). The pharmaceutical form is designated as PHF00165MIG. The maximum daily and total dose is 0.3 mg, administered intrathecally. The treatment period is limited to one day. Participant compliance will be monitored to ensure adherence to the dosing schedule.

**Lidocaine**, in the form of anhydrous lidocaine hydrochloride, is used as a comparator treatment. The pharmaceutical form is PHF00231MIG, and it is administered intravenously. The maximum daily and total dose is 1500 mg, with a treatment period of one day. Compliance monitoring will be conducted to ensure proper administration and adherence to the dosing regimen.

**Bupivacaine**, combined with adrenaline acid tartrate BP, is another test treatment in the study. The pharmaceutical form is PHF00231MIG, and it is administered intrathecally. The maximum daily and total dose is 20 mg, with a treatment period of one day. Participant compliance will be monitored to ensure correct dosing and administration.

Efficacy in this clinical trial will be assessed using the **Quality of Recovery 15 (QoR-15)** score, which is a patient-centered outcome scale. The primary endpoint is the QoR-15 score at postoperative day 1. Secondary endpoints include the QoR-15 score preoperatively and at postoperative day 2, as well as various measures of pain using the Numeric Rating Scale (NRS) at different time points, such as 2 hours after arrival to the Post Anesthesia Care Unit (PACU), on postoperative days 1 to 3, and at rest and during motion on postoperative day 7.

Additional secondary endpoints encompass a range of postoperative recovery parameters, including the time from arrival in the operating room to the start of surgery, the time from the end of surgery until leaving the operating room, and the incidence of unplanned termination of lidocaine infusion. The study will also measure the amount of remifentanil and other opioids administered intraoperatively and postoperatively, the length of stay at the PACU, and the incidence of postoperative nausea and vomiting (PONV) requiring treatment at specified intervals.

Further assessments will include "time out-of-bed" on postoperative days 1 to 3, the first postoperative day passing gases and stool, the incidence of pruritus, the length of stay and days alive and out of hospital within 30 days (DAOH30), and postoperative complications until postoperative day 30. The requirement for opioids after discharge and the incidence of respiratory depression leading to the use of a mu-antagonist within 48 hours of anesthesia induction will also be evaluated.

Intraoperative parameters such as fluid balance, time with low blood pressure, mean arterial pressure (MAP) variations, norepinephrine usage, and various cardiac indices will be monitored. Biochemical markers of inflammation will also be assessed to provide a comprehensive evaluation of the efficacy of the interventions in improving postoperative recovery.