A Study on Reducing Opioid Use After Ankle Arthroscopy

Effect of a Postoperative Multimodal Analgesic Protocol Predominantly Based on Non-Opioid Medications vs Opioid-Based Analgesia on Pain After Ankle Arthroscopy: A Noninferiority Randomized Clinical Trial

Study Title Effect of a Postoperative Multimodal Analgesic Protocol Predominantly Based on Non-Opioid Medications vs Opioid-Based Analgesia on Pain After Ankle Arthroscopy: A Noninferiority Randomized Clinical Trial

Purpose This study aims to compare the pain control effect and side effects of non-opioid versus opioid medications in patients undergoing ankle arthroscopy. The goal is to find a safer analgesic strategy to reduce opioid use and related risks (e.g., addiction, respiratory depression) while maintaining effective postoperative pain management.

Design Study Type: Prospective, randomized controlled trial. Participants: 110 adults (18-65 years) scheduled for ankle arthroscopy under general anesthesia.

Interventions:

Experimental Group: Non-opioid regimen (celecoxib + acetaminophen). Control Group: Opioid regimen (oxycodone + acetaminophen). Assessments: Pain scores (NRS) at 2 hours,6 hours,12 hours, 24 hours, and days 2-6 postoperatively; Area under the curve (AUC\_{0-24}) of Numerical Rating Scale (NRS) pain intensity scores from 0-24 hours.adverse events (e.g., nausea, constipation); The total consumption of additional rescue opioids, expressed as oral morphine equivalent dose (OME); patient satisfaction.

Key Eligibility Able to provide informed consent. ASA physical status I-II. BMI 16-32 kg/m². Exclusion criteria: Chronic pain, opioid use history, allergies to study drugs, or severe organ dysfunction.

Benefits & Risks Benefits: Standardized analgesia management and personalized pain monitoring; potential contribution to safer clinical pain protocols.

Risks: Opioids may cause nausea, sedation, or respiratory depression; non-opioids may carry risks of gastrointestinal bleeding or liver injury. Emergency support is available for severe events.

Contact Information

For more details, contact the research team at Zhejiang University Second Affiliated Hospital:

Phone: 0571-87783759 Email: keyanlunli_zheer@163.com This trial is registered to evaluate non-opioid alternatives for ankle arthroscopy pain control, prioritizing patient safety and evidence-based care.

Study Overview

• Status: Completed
• Conditions: Ankle Sprain; Talus Osteochondral Defect; Non-Opioid Pain Management; Ankle (Ligaments); Instability (Old Injury); Opioid Analgesia
• Intervention / Treatment: Drug: Non-opioid analgesic regimen; Drug: Opioid Analgesic Regimen

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-65 years old. Scheduled for elective ankle arthroscopy under general anesthesia(Arthroscopic procedures including：(1) debridement procedures, including synovectomy, removal of loose bodies, and treatment of soft-tissue or bony impingement; (2) cartilage-related procedures, including debridement, microfracture, or other bone marrow stimulation techniques for osteochondral lesions of the talus; and (3) ligamentous procedures, including arthroscopically assisted repair or reconstruction for chronic lateral ankle instability).

American Society of Anesthesiologists (ASA) physical status I or II. Body mass index (BMI) 16-32 kg/m². Able to understand and sign the informed consent form. Willing and able to comply with study procedures, including follow - up visits and outcome assessments.

Exclusion Criteria:

• History of chronic pain (pain lasting >3 months) or current use of opioid medications within the past 3 months.

Known allergies or contraindications to study medications (celecoxib, acetaminophen, oxycodone, tramadol, dezocine).

Severe cardiovascular, hepatic, renal, or respiratory dysfunction (ASA ≥ III). History of substance abuse, alcohol dependence, or significant psychiatric disorders.

Pregnant or breastfeeding women. Participation in another clinical trial within the past 30 days. Unstable medical conditions that may interfere with study participation or outcome assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-Opioid Analgesia Group; Participants in this group will receive a multimodal non - opioid analgesic regimen. The treatment includes celecoxib(Flurbiprofen axetil) and acetaminophen(Jingxin (a Chinese pharmaceutical company)), aiming to provide effective pain relief while reducing the use of opioids and minimizing associated risks such as addiction, respiratory depression, and gastrointestinal adverse events during the perioperative period of ankle arthroscopy.	Drug: Non-opioid analgesic regimen; Immediately after surgery, patients will receive oral acetaminophen 500 mg plus celecoxib 400 mg. Thereafter, celecoxib 200 mg BID and acetaminophen 500 mg Q6H will be administered. Rescue analgesia protocol: a limited rescue prescription of oxycodone/acetaminophen (containing 5 mg oxycodone), to be taken every 2 hours as needed, with no more than 10 tablets per day, and only if adequate pain relief is not achieved (defined as NRS score ≥ 4).
Active Comparator: Opioid Analgesia Group; This group will be administered an opioid - based regimen with oxycodone - acetaminophen(Parecoxib). It represents the usual clinical practice for postoperative pain control and serves as a reference to compare the efficacy and safety of the non - opioid regimen in managing pain after ankle arthroscopy.	Drug: Opioid Analgesic Regimen; Participants will take 5 mg/325 mg of oxycodone - acetaminophen every 6 hours as needed for pain, with a maximum of 4 doses per day. Rescue analgesia protocol: a limited rescue prescription of oxycodone/acetaminophen (containing 5 mg oxycodone), to be taken every 2 hours as needed, with no more than 10 tablets per day, and only if adequate pain relief is not achieved (defined as NRS score ≥ 4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score at 24 hours post-operation	The pain score will be assessed using the Numeric Rating Scale (NRS), where 0 represents "no pain" and 10 represents "the worst pain imaginable." This score reflects the patient's subjective experience of pain intensity 24 hours after ankle arthroscopy. By comparing the NRS scores between the non - opioid analgesia group and the opioid analgesia group, we can evaluate the effectiveness of each intervention in managing acute postoperative pain.	24 hours after ankle arthroscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC\_{0-24}) of Numerical Rating Scale (NRS) pain intensity scores from 0-24 hours.	The area under the curve (AUC) of NRS pain scores within the first 24 hours will be calculated using NRS measurements at 2, 6, 12, and 24 hours postoperatively, providing an accurate estimate of the patient's overall pain experience during the 24-hour period.	Within 24 hours postoperatively
The total consumption of additional rescue opioids, expressed as oral morphine equivalent dose (OME)	This indicator reflects whether pain control in the non-opioid group is adequate. If pain control is insufficient, patients will consume more opioids for rescue, thereby allowing an inference on the analgesic efficacy of the non-opioid regimen.	From immediately after surgery until 6 days post - operation
Incidence of adverse events	Adverse events related to the analgesic regimens will be recorded, including but not limited to nausea, vomiting, constipation, dizziness, sedation, respiratory depression, and gastrointestinal bleeding. The occurrence rate of each adverse event will be calculated for both groups to evaluate the safety profiles of the non - opioid and opioid interventions.	From the start of medication administration until 6 days post - operation
Patient - reported satisfaction	Participants will complete a 4-point likert scale to describe his satisfaction of the pain manegement at 6 days post - operation. The questionnaire assesses patients' overall satisfaction with the pain management strategy, including aspects such as effectiveness of pain relief, tolerability of medications, and impact on daily activities. Scores range from 1 (extremely dissatisfied) to 4 (extremely satisfied).	6 days post - operation
Patient - reported outcome measures (PROMIS) scores	Participants will fill out the PROMIS Pain Interference - Short Form (PI - SF) . it evaluate the impact of pain on daily function , respectively. Scores are standardized, with higher values indicating greater interference or disturbance.	Baseline (pre - operation), and 6 days post - operation
Pain score on the second postoperative day	Pain intensity will be evaluated using the Numeric Rating Scale (NRS, 0 = no pain, 10 = worst pain imaginable) at second postoperative day. the scores help to comprehensively assess the time - course of pain relief provided by each intervention.	2 hours post - operation; 2 - 6 days post - operation
Pain score on the third postoperative day	Pain intensity will be evaluated using the Numeric Rating Scale (NRS, 0 = no pain, 10 = worst pain imaginable) at third postoperative day. the scores help to comprehensively assess the time - course of pain relief provided by each intervention.	the third postoperative day
Pain score on the forth postoperative day	Pain intensity will be evaluated using the Numeric Rating Scale (NRS, 0 = no pain, 10 = worst pain imaginable) at forth postoperative day. the scores help to comprehensively assess the time - course of pain relief provided by each intervention.	the forth postoperative day
Pain score on the fifth postoperative day	Pain intensity will be evaluated using the Numeric Rating Scale (NRS, 0 = no pain, 10 = worst pain imaginable) at fifth postoperative day. the scores help to comprehensively assess the time - course of pain relief provided by each intervention.	on the fifth postoperative day
Pain score on the sixth postoperative day	Pain intensity will be evaluated using the Numeric Rating Scale (NRS, 0 = no pain, 10 = worst pain imaginable) at sixth postoperative day. the scores help to comprehensively assess the time - course of pain relief provided by each intervention.	the sixth postoperative day
Insomnia Severity Index	To assess the subjective severity of insomnia before and after surgery, its impact on daytime functioning, and the degree of distress caused by sleep problems.	Baseline (pre - operation), and 6 days post - operation

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Actual): May 1, 2026
• Study Completion (Actual): May 7, 2026

Study Registration Dates

• First Submitted: July 10, 2025
• First Submitted That Met QC Criteria: August 26, 2025
• First Posted (Actual): September 4, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Ankle Injuries
• Other Study ID Numbers: 2025-0286

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No