Determination of the Effective Dose of a Single Intravenous Dose of Tegileridine Fumarate for Postoperative Analgesia After Orthopedic Surgery: A Up-and-Down Sequential Allocation Study

The goal of this clinical trial is to determine the 90% effective dose (ED90) of a single intravenous injection of tegileridine fumarate for postoperative analgesia in adult patients aged 18-75 years with American Society of Anesthesiologists (ASA) physical status I-III undergoing orthopedic surgery, including spinal fusion surgery, femoral fracture fixation, and total knee arthroplasty.

The main questions this study aims to answer are:

What is the ED90 of a single intravenous dose of tegileridine fumarate for achieving adequate postoperative analgesia, defined as a Numeric Rating Scale (NRS) pain score ≤ 3 within 30 minutes after awakening from anesthesia without the need for rescue analgesia?

Participants will:

Receive a single intravenous injection of tegileridine fumarate during skin closure at the end of surgery.

Start with an initial dose of 0.5 mg, with subsequent doses adjusted upward or downward in 0.1 mg increments for the next participant based on the analgesic response of the preceding participant, following a biased-coin up-and-down sequential dose allocation design.

Be closely monitored during the postoperative recovery period for pain intensity, vital signs (including heart rate, blood pressure, respiratory rate, and oxygen saturation), and adverse reactions such as nausea, vomiting, respiratory depression, agitation, and other opioid-related side effects.

This study aims to identify an optimal single-dose regimen of tegileridine fumarate that provides effective postoperative analgesia with an acceptable safety profile, thereby improving postoperative pain control and promoting enhanced recovery in patients undergoing orthopedic surgery.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Single intravenous injection of Tegileridine Fumarate

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Min Yin Study Coordinator, Doctor; Phone Number: 15888210247; Email: zryanmin@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hanzhong, Zhejiang, China, 3100000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University anesthesiology department
      • Contact: yan min doctor; Phone Number: 15888210247; Email: zryanmin@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 to 75 years.
• Scheduled for elective orthopedic surgery, including spinal fusion, femoral fracture fixation, or total knee arthroplasty.
• American Society of Anesthesiologists (ASA) physical status I-III.
• Ability to understand the study procedures and provide written informed consent.

Exclusion Criteria:

• Patients with moderate to severe obesity (BMI > 30 kg/m²).
• Known hypersensitivity or allergy to tegileridine fumarate or other analgesics.
• History of chronic pain or long-term use of opioids.
• Severe hepatic or renal impairment.
• Patients requiring postoperative ICU care.
• Severe respiratory depression (e.g., oxygen saturation < 90%).
• Known or suspected gastrointestinal obstruction, including paralytic ileus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single intravenous Tegileridine Fumarate arm

Drug: Single intravenous injection of Tegileridine Fumarate; Single intravenous injection of tegileridine fumarate for postoperative analgesia in adult patients (18-75 years, ASA I-III) undergoing orthopedic surgery, including spinal fusion, femoral fracture fixation, and total knee arthroplasty. The study uses a dose-escalation design to determine the 90% effective dose (ED90). Doses: To be determined using an up-and-down sequential allocation method (dose-ranging study).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective dose producing adequate postoperative analgesia in 90% of patients (ED90)	The primary outcome was the 90% effective dose (ED90) of a single intravenous bolus of tegileridine for postoperative analgesia following orthopedic surgery. Analgesic success was defined as a Numeric Rating Scale (NRS) pain score ≤ 3 within 30 minutes after awakening from anesthesia without the need for rescue analgesics. Dose allocation followed a biased-coin up-and-down sequential design, with dose adjustments based on the analgesic response of the preceding patient. The ED90 and its 90% confidence interval were estimated using isotonic regression analysis.	Within 30 minutes after awakening from anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of postoperative nausea and vomiting (PONV)	The incidence and severity of postoperative nausea and vomiting (PONV) within 24 hours after administration of tegileridine were assessed. PONV was evaluated by trained clinical staff using a standardized ordinal severity scale, defined as: 0 = no nausea or vomiting; = nausea only;; = retching (dry heaves);; = vomiting.	From drug administration to 24 hours postoperatively
Heart rate (HR)	Measured in beats per minute (bpm).	From immediately before drug administration to 24 hours postoperatively
Respiratory Rate (RR)	Measured in breaths per minute (bpm).	From immediately before drug administration to 24 hours postoperatively
Peripheral Oxygen Saturation (SpO₂)	Measured as a percentage (%).	From immediately before drug administration to 24 hours postoperatively
Extubation-related airway responses	Incidence of airway reactions during emergence from anesthesia, including coughing and laryngospasm, assessed by the attending anesthesiologist at the time of tracheal extubation.	From extubation until 10 minutes after extubation
Postoperative rescue analgesia requirement	Use of rescue analgesia after surgery, including whether additional opioid analgesics were required within 30 minutes after awakening and cumulative opioid consumption within 24 hours postoperatively (converted to morphine equivalents).	From awakening to 24 hours postoperatively
Patient-controlled analgesia (PCA) usage	PCA usage parameters, including number of effective and total PCA button presses and total PCA-delivered opioid dose within 24 hours after surgery.	From awakening to 24 hours postoperatively
Postoperative pain intensity (NRS scores)	Pain intensity assessed using the Numeric Rating Scale (NRS, 0-10; 0 = no pain, 10 = worst imaginable pain) at rest and during movement at predefined postoperative time points.	30 minutes, 6 hours, 12 hours, and 24 hours after awakening
Incidence of postoperative adverse events	Incidence of adverse events, including agitation (Richmond Agitation-Sedation Scale ≥2), delirium (Nu-DESC score ≥2), respiratory depression (SpO₂ <90%), delayed emergence, pruritus, dizziness, shivering, and postoperative nausea and vomiting (PONV), graded according to severity.	From drug administration to 24 hours postoperatively

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative
• Other Study ID Numbers: 2025-0393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No