Methadone in TKA for Post-op Pain and Opioid Reduction

Reduction of Post-op Pain and Opioid Consumption With the Addition of Methadone in Total Knee Arthroplasty: a Double-blind Randomized Control Trial

This randomized, double-blind controlled trial investigates whether intraoperative IV methadone (0.15 mg/kg based on ideal body weight) reduces acute postoperative pain and opioid consumption in patients undergoing elective total knee arthroplasty under spinal anesthesia with mepivacaine.

Study Overview

• Status: Recruiting
• Conditions: Post Operative Pain
• Intervention / Treatment: Drug: Methadone Hydrochloride

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Haley Nitchie, MHA; Phone Number: 843-792-1869; Email: nitchie@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Haley Nitchie, MHA; Phone Number: 843-792-1869; Email: nitchie@musc.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion

• Ages 18-75 years of age
• Undergoing elective primary total knee arthroplasty with mepivacaine in the spinal anesthesia

Exclusion

• Allergy to methadone or mepivacaine
• Severe liver disease defined as Child's Pugh Class C
• End stage renal disease requiring dialysis
• Known diagnosis of prolonged QT syndrome
• Currently pregnant
• Unable to provide written, informed consent
• Non-English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methadone; Patients will intraoperatively receive methadone 0.15mg/kg IV, based on ideal body weight.	Drug: Methadone Hydrochloride; Patients will intraoperatively be administered methadone 0.15mg/kg IV, based on ideal body weight.
No Intervention: No Methadone; Patients will NOT receive methadone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported pain in the recovery unit after surgery	Patient reported pain on a Visual Analog Scale (VAS) from 0-100mm at approximately 30-60 minutes after arriving to the recovery unit after surgery. A lower pain score means a better outcome.	up to 24 hours after surgery ends

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Consumption in the recovery unit	Opioid consumption measured in oral morphine milligram equivalents (MMEs) while the patient is in the PACU (Post-Anesthesia Recovery Unit).	PACU Arrival until PACU Discharge up to 30 days
Time to first opioid rescue dose	Measured from the PACU arrival time, to the time the first opioid rescue dose is given while in the PACU.	up to 24 hours after surgery ends
Pain scores	Visual Analog Score (VAS) 0-100mm reporting pain at rest, and with movement. A lower pain score means a better outcome.	PACU, 24 hours, 48 hours, and 72 hours post-operatively.
Postoperative nausea and/or vomiting	Incidence of postoperative nausea and/or vomiting after surgery as reported by the patient.	PACU through 72 hours post-operatively
Quality of Recovery	Change in quality of recovery score from baseline to 24-hours post-operatively measured using the Quality of Recovery 15 Assessment (QoR-15). This assessment is scored 0-150, with a higher score indicating a better quality of recovery. Each of the 15 questions is on an 11-point numerical rating scale from 0-10, and the selections are added together to result in the total score.	up to 24-hours post-operatively

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: William Barrett, M.D., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2026
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: November 6, 2025
• First Submitted That Met QC Criteria: November 6, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: post-operative pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Ketones; Methadone
• Other Study ID Numbers: Pro00147447

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