A RCT Using Methadone in the Management of Post-Operative Pain in Total Knee Replacement

A Prospective, Randomized Trial Utilizing Methadone in the Management of Post-Operative Pain in Total Knee Replacement

The goal of this study is to determine whether one dose of IV methadone given right before surgery will help patients' pain management after a total knee replacement and reduce the amount of pain medications taken in the weeks after surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: Methadone

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Makenna Hemmerle; Phone Number: 303-260-2951; Email: makenna.hemmerle@adventhealth.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent from
2. Stated willingness to comply with all study procedures and availability to attend all required visits for the duration of the study.
3. Age 21- 75
4. Unilateral total knee arthroplasty at Colorado Joint Replacement
5. All individuals will be screened for drug use (opioid use, illicit drug use) at their preoperative appointment
6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

Exclusion Criteria:

1. Narcotic use in the past 6 weeks
2. Current or previous history of drug and alcohol abuse
3. Tobacco use in the previous 90 days
4. Treatment with another investigational drug
5. Patients that cannot receive spinal anesthesia
6. Patients that cannot receive the standardized multimodal pain medications (i.e. Tylenol, gabapentin and meloxicam)'
7. Patients that are not able to go home after leaving the hospital and require a short-term rehabilitation facility
8. Obstructive sleep apnea
9. Morbid obesity (BMI >40)
10. Patients with liver disease.
11. Significant kidney disease - stage 3 CKD or greater
12. Pregnant or nursing females
13. Baseline QTc >480
14. severe COPD (GOLD 3 or 4)
15. home oxygen requirement

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
Experimental: Methadone; Patient will receive one perioperative dose of IV methadone prior to their surgical procedure in addition to standard of care medications.	Drug: Methadone; Subjects randomized to receive methadone will be given one dose of methadone 0.15mg/kg intravenously dosed based on ideal body weight administered by the anesthesia team prior to surgical incision
No Intervention: No medication; Patient will not receive only the standard of care medications for their procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid use for 48 hours post-operatively	Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.	48 hours after TKA procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Defense and Veterans Pain Scale	Patients will keep a log to track their pain after surgery on a scale of 0-10.	2 weeks after TKA procedure
Opioid-Related Symptom Distress Scale (ORSDS)	Patients will complete the survey to track opioid-related side effects	2 weeks after TKA procedure
Pittsburgh Sleep Quality Index	Patients will complete survey to monitor sleeping habits	2 weeks after TKA procedure
Total opioid usage over 2 weeks post-operatively	Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.	2 weeks after TKA procedure
Knee Society Score	Patient reported outcome	2 weeks after TKA procedure
KOOS-12 Knee Survey	Patient reported outcome	2 weeks after TKA procedure
Veterans Rand 12-Item Health Survey (VR-12)	Patient reported outcome	2 weeks after TKA procedure

Collaborators and Investigators

• Sponsor: AdventHealth

Publications and helpful links

General Publications

• Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.
• Cancienne JM, Patel KJ, Browne JA, Werner BC. Narcotic Use and Total Knee Arthroplasty. J Arthroplasty. 2018 Jan;33(1):113-118. doi: 10.1016/j.arth.2017.08.006. Epub 2017 Aug 17.
• Menendez ME, Ring D, Bateman BT. Preoperative Opioid Misuse is Associated With Increased Morbidity and Mortality After Elective Orthopaedic Surgery. Clin Orthop Relat Res. 2015 Jul;473(7):2402-12. doi: 10.1007/s11999-015-4173-5. Epub 2015 Feb 19.
• Komen H, Brunt LM, Deych E, Blood J, Kharasch ED. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Anesth Analg. 2019 Apr;128(4):802-810. doi: 10.1213/ANE.0000000000003464.
• Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
• Friesgaard KD, Brix LD, Kristensen CB, Rian O, Nikolajsen L. Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial. BJA Open. 2023 Aug 5;7:100219. doi: 10.1016/j.bjao.2023.100219. eCollection 2023 Sep.
• Li WT, Bell KL, Yayac M, Barmann JA, Star AM, Austin MS. A Postdischarge Multimodal Pain Management Cocktail Following Total Knee Arthroplasty Reduces Opioid Consumption in the 30-Day Postoperative Period: A Group-Randomized Trial. J Arthroplasty. 2021 Jan;36(1):164-172.e2. doi: 10.1016/j.arth.2020.07.060. Epub 2020 Jul 30.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: methadone; pain management; TKA
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Organic Chemicals; Ketones; Methadone
• Other Study ID Numbers: 2387801

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.: No