Randomized, Blinded Study of Neostigmine/Glycopyrronium Bromide vs. Sugammadex for Reversal of Neuromuscular Blockade in Patients Aged ≥75 Undergoing Laparoscopic Surgery

The primary objective of this study is to evaluate the time to achieve a train-of-four (TOF) ratio of ≥ 0.9 following administration of either **neostigmine**/glycopyrrolate at a dose of 50 micrograms per kilogram or **sugammadex** at a dose of 2 milligrams per kilogram in patients aged 75 years and older. This is clinically relevant as achieving a TOF ratio of ≥ 0.9 is indicative of adequate recovery from neuromuscular blockade, which is crucial for patient safety and optimal recovery post-anaesthesia, particularly in elderly patients undergoing laparoscopic robot-assisted surgery. The hypothesis posits that sugammadex will provide a faster recovery time compared to neostigmine/glycopyrrolate, potentially offering a more efficient reversal of neuromuscular blockade in this patient population.

The clinical trial involves participants aged **75 years and older**, both male and female, who are scheduled for robotic-assisted laparoscopic surgery under general anesthesia. The study population is characterized by individuals with an **American Society of Anesthesiologists (ASA) physical status classification** ranging from I to IV, indicating a wide range of general health statuses from healthy to those with severe systemic disease. Participants must be able to read and understand Danish, and they have provided informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The study focuses on the effects of anesthesia in the context of laparoscopic robot-assisted surgery, specifically comparing the time to achieve a train-of-four (TOF) ratio of ≥ 0.9 using either neostigmine/glycopyrrolate or sugammadex. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of two reversal agents, **neostigmine**/**glycopyrrolate** and **sugammadex**, in reversing neuromuscular blockade in patients aged 75 years and older undergoing robotic-assisted laparoscopic surgery. The primary objective is to determine the time to achieve a train-of-four (TOF) ratio of ≥ 0.9 following administration of the reversal agents. The trial is expected to commence on August 12, 2024, and conclude by March 31, 2025, with recruitment starting on June 1, 2023.

Participants will be involved in the study for a maximum of one day, corresponding to the duration of their surgical procedure and immediate recovery period. The study includes several key visits: an initial **screening** visit to confirm eligibility based on criteria such as age, informed consent, and scheduled surgery under general anesthesia; the **treatment** visit, where the reversal agent is administered; and the **end-of-study** visit, which occurs post-surgery to assess primary and secondary endpoints. Follow-up assessments will be conducted to monitor for signs of residual neuromuscular blockade and any adverse events, such as episodes of desaturation or cardiac arrhythmias, within 180 minutes post-administration of the reversal agent.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial's primary endpoint is the time to TOF > 0.9, while secondary endpoints include the assessment of residual neuromuscular blockade and other safety parameters. The study aims to provide valuable insights into the comparative effectiveness of the two reversal agents in an elderly population, with results expected to be published within 12 months of trial completion.

The clinical trial involves the administration of two **experimental medications** for the reversal of neuromuscular blockade in elderly patients aged 75 years and older. The first medication is Robinul-Neostigmin, a **solution for injection** containing the active substances **glycopyrronium bromide** and **neostigmine methylsulfate**. This medication is administered intravenously at a dosage of 50 micrograms per kilogram (µg/kg). The maximum daily and total dose is 50 µg/kg, with a treatment period limited to one day. The pharmaceutical form is a solution for injection, and the product is manufactured by Viatris APS. The role of this medication in the trial is as a comparator.

The second medication used in the trial is Bridion, a 100 mg/mL solution for injection containing the active substance **sugammadex**. This medication is also administered intravenously, with a dosage of 2 milligrams per kilogram (mg/kg). The maximum daily and total dose is 16 mg/kg, and the treatment period is similarly restricted to one day. Bridion is produced by Merck Sharp & Dohme BV and serves as the test medication in the trial. Both medications are chemically derived and are not formulated for pediatric use. The trial aims to compare the time to achieve a train-of-four (TOF) ratio of ≥ 0.9 between the two treatments, with the hypothesis that sugammadex provides a faster recovery time compared to neostigmine/glycopyrrolate.

Efficacy in this clinical trial will be assessed primarily by measuring the time to achieve a train-of-four (TOF) ratio of ≥ 0.9 following the administration of either **neostigmine/glycopyrrolate** or **sugammadex** in patients aged 75 years and older. This primary endpoint will be evaluated from the beginning of the administration of the reversal agent until the TOF ratio exceeds 0.9. The hypothesis is that sugammadex 2 mg/kg will result in a faster time to TOF ≥ 0.9 compared to neostigmine/glycopyrrolate 50 µg/kg.

Secondary efficacy endpoints include the assessment of residual neuromuscular blockade within 90 minutes after the administration of the reversal agent. This will be evaluated using a composite of clinical signs such as hand grip strength, occurrence of double or blurred vision, ability to track objects with eyes, ability to sustain a head lift, and ability to protrude the tongue. Additional secondary endpoints include the occurrence of desaturation episodes, new cardiac arrhythmias, reintubation, and the time from administration of the reversal agent to when the patient is ready to leave the operating room. These parameters will be assessed at specific time points, including upon arrival at the post-anesthesia care unit (PACU) after 20 minutes and again after 90 minutes.