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.

Inclusion criteria

• Aged 10 years to less than 18 years.
• Scheduled to undergo posterior spinal fusion (PSF) surgery for scoliosis under general anesthesia.
• American Society of Anesthesiologists (ASA) physical status classification I to III.
• The participant and their parent or legal guardian voluntarily provide written informed consent prior to any study-related procedures.

Exclusion criteria

• History of difficult airway, severe respiratory depression (SpO₂ < 90%), acute or severe bronchial asthma.
• History of severe cardiovascular or cerebrovascular disease, such as myocardial infarction, unstable angina, second-degree or higher atrioventricular block, NYHA Class III or higher heart failure, or stroke.
• Known or suspected gastrointestinal obstruction, including paralytic ileus.
• Known hypersensitivity to opioids or any component of the study drug formulation.
• History of psychiatric disorders (e.g., schizophrenia, depression) or cognitive impairment.
• Diagnosis of neuromuscular scoliosis or presence of any other chronic pain condition that may interfere with postoperative pain assessment.
• Chronic use of opioid analgesics or use of any analgesic medication within 48 hours prior to surgery.
• Planned postoperative admission to the intensive care unit (ICU).
• Any other condition deemed by the investigator to be inappropriate for participation in the study.