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

June 16, 2026 updated by: AdventHealth

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

192

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 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
Time Frame: 48 hours after TKA procedure
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
Total opioid usage over 2 weeks post-operatively
Time Frame: 2 weeks after TKA procedure
Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.
2 weeks after TKA procedure
Defense and Veterans Pain Scale
Time Frame: 2 weeks after TKA procedure
Using the Defense and Veterans Pain Scale, patients will rate their pain ranging from 0 (no pain) to 10 (severe pain)
2 weeks after TKA procedure
Opioid-Related Symptom Distress Scale (ORSDS)
Time Frame: At baseline and 2 weeks after TKA procedure
4-point scale that evaluates 12 symptoms in 3 symptom categories including frequency, severity, and bothersomeness. The ORSDS may be used to calculate a symptom-specific score, which is the average of the 3 symptom distress dimensions and range from 0 to 4. The composite ORSDS score is the mean of all 12 symptom-specific scores. Composite ORSDS scores range from 0 to 4.
At baseline and 2 weeks after TKA procedure
Pittsburgh Sleep Quality Index
Time Frame: At baseline and 2 weeks after TKA procedure
Patients will complete survey to monitor sleeping habits
At baseline and 2 weeks after TKA procedure
Knee Society Score
Time Frame: At baseline
This survey includes alignment, instability, joint range of motion, and symptoms. A higher score indicates good alignment, range of motion, and minimal symptoms of pain. A lower score indicates poor knee alignment, potential issues in range of motion, and the likely experience of symptoms of pain.
At baseline
KOOS-12 Knee Survey
Time Frame: At baseline
This survey is used to evaluate knee pain, function and quality of life. The total score ranges from 0 to 100, where higher scores indicate better outcomes.
At baseline
Veterans Rand 12-Item Health Survey (VR-12)
Time Frame: At baseline
This survey assesses overall health-related quality of life across physical and mental domains. It generates two summary scores-Physical Component Summary (PCS) and Mental Component Summary (MCS)-to provide a standardized evaluation of a patient's functional health and well-being.
At baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

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)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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