Overview
The goal of this clinical trial is to see if a new pain medicine called Tegileridine is at least as effective as morphine (the standard treatment) for pain relief after spinal surgery in teenagers with scoliosis. This type of study is called a "non-inferiority" trial. The study will also carefully compare the safety of both medicines.
The main questions it aims to answer are:
Is Tegileridine no worse than morphine at controlling pain in the first 24 hours after surgery? How do the side effects (like sleepiness or nausea) of Tegileridine compare to those of morphine? Researchers will compare two different doses of Tegileridine against morphine. Neither the participants nor the doctors assessing them will know which medicine is being given.
Participants in this study will:
Receive one of the three pain medicine options through a pump (called a PCA pump) that they can control themselves after surgery.
Use the pump for up to 48 hours. Regularly rate their pain levels using a simple number scale. Have their health closely monitored by the study team during this time.
Description
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.
Eligibility
Inclusion Criteria:
- Aged 10 years to less than 18 years.
- Scheduled to undergo posterior spinal fusion (PSF) surgery for adolescent idiopathic 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:
- Baseline room-air oxygen saturation (SpO2) \< 90% at rest, 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.
- Severe cognitive impairment or uncontrolled psychiatric disorders (e.g., active schizophrenia) that preclude the patient's ability to comprehend the NRS or independently operate the patient-controlled analgesia (PCA) pump.
- 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 long-acting analgesics within 48 hours prior to surgery (short-acting non-opioid analgesics are permitted but must be discontinued at least 12 hours preoperatively).
- Planned postoperative admission to the intensive care unit (ICU).
