Tegileridine for Postoperative Pain After Adolescent Scoliosis Surgery

This is a prospective, multicentre, randomized, double-blind, controlled, non-inferiority clinical trial designed to evaluate the efficacy and safety of Tegileridine for postoperative analgesia in adolescent patients undergoing spinal fusion surgery for scoliosis.

Postoperative pain management is crucial for recovery, with opioids like morphine being the standard of care. However, morphine is associated with significant side effects, including respiratory depression, nausea, and vomiting. Tegileridine is a novel, highly selective μ-opioid receptor agonist that is hypothesized to provide potent analgesia with an improved safety profile, particularly regarding respiratory depression.

A total of 171 adolescent patients (aged 10 to \<18 years) scheduled for surgery will be enrolled. Participants will be randomly assigned in a 1:1:1 ratio to one of three treatment groups:

Group T1: Tegileridine 20 μg/kg loading dose, followed by patient-controlled analgesia (PCA) at a dose of 1 μg/kg per bolus.

Group T2: Tegileridine 20 μg/kg loading dose, followed by PCA at a dose of 2 μg/kg per bolus.

Group M (Active Comparator): Morphine 60 μg/kg loading dose, followed by PCA at a dose of 20 μg/kg per bolus.

The study medication will be prepared by an unblinded nurse not involved in subsequent patient care or assessment. Upon arrival in the post-anesthesia care unit (PACU) after surgery, the assigned loading dose of the study drug will be administered, immediately followed by the initiation of the PCA pump, which will be maintained for 48 hours. To maintain blinding, the study drugs are diluted in normal saline to appear identical. Patients, attending anesthesiologists, and outcome assessors will all be blinded to the treatment assignment.

The primary objective is to demonstrate the non-inferiority of Tegileridine to morphine in terms of analgesic efficacy. The primary efficacy endpoint is the area under the curve (AUC) of resting pain intensity scores, measured on an 11-point Numerical Rating Scale (NRS), over the first 24 hours after initiating PCA. A predefined non-inferiority margin of 12 will be used for the comparison. Statistical testing will follow a hierarchical procedure, first comparing the T2 group to the morphine group, and if non-inferiority is established, proceeding to compare the T1 group to morphine.

Secondary objectives include comparing the groups on various efficacy measures, such as pain AUC at other time points, rescue analgesic consumption, and patient satisfaction. Safety objectives focus on the incidence and severity of adverse events, with continuous monitoring for postoperative hypoxemia (SpO₂ \< 90%), assessment of sedation levels using the modified Pasero Opioid-induced Sedation Scale (m-POSS), and recording of other common opioid-related side effects like postoperative nausea and vomiting (PONV).

The primary analysis will be conducted on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). Sensitivity analyses and a pre-specified subgroup analysis by gender are also planned.

• Area Under the Curve (AUC) of Resting Pain Scores on the Numerical Rating Scale (NRS) Over Multiple Time Intervals [Срок оценки: The AUC will be calculated for the cumulative intervals from PCA initiation up to 6 hours, 12 hours, and 48 hours post-initiation.]
• Area Under the Curve (AUC) of Activity-Induced Pain Scores on the Numerical Rating Scale (NRS) over Multiple Intervals [Срок оценки: Assessed at 6, 12, 24, and 48 hours after PCA initiation.]
• Resting and Activity-Induced Pain Scores on the Numerical Rating Scale (NRS) at Multiple Time Points [Срок оценки: Assessed at 16 predefined time points from 5 minutes to 48 hours after PCA initiation.]
• Proportion of Participants Requiring Rescue Analgesia [Срок оценки: From PCA initiation up to 48 hours post-initiation.]
• Time to First Use of Rescue Analgesia [Срок оценки: From PCA initiation up to 48 hours post-initiation (time to event is measured).]
• Total Number of Rescue Analgesic Administrations Per Participant [Срок оценки: From PCA initiation up to 48 hours post-initiation.]
• Cumulative Dose of Rescue Analgesic Medication [Срок оценки: From PCA initiation up to 48 hours post-initiation.]
• Proportion of Participants with Pain NRS Score ≤ 3 at Each Assessment Time Point [Срок оценки: Assessed at 16 predefined time points from 5 minutes to 48 hours after PCA initiation.]
• Total Number of PCA Pump Attempts and Successful Deliveries [Срок оценки: From PCA initiation up to 48 hours post-initiation.]
• Postoperative Length of Hospital Stay [Срок оценки: From the day of surgery to the day of hospital discharge, an average of 10 days.]
• Satisfaction with Pain Treatment [Срок оценки: At 30 minutes after stopping PCA (typically around 48 hours post-surgery).]
• Incidence of Postoperative Hypoxemia [Срок оценки: From PCA initiation up to 48 hours post-initiation.]