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

NCT07485803 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 2387801
• Study Type: interventional
• Target: 192
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Total Knee Arthroplasty

Keywords

pain management; TKA; methadone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Defense and Veterans Pain Scale

  2 weeks after TKA procedure

• Opioid-Related Symptom Distress Scale (ORSDS)

  2 weeks after TKA procedure

• Pittsburgh Sleep Quality Index

  2 weeks after TKA procedure

• Total opioid usage over 2 weeks post-operatively

  2 weeks after TKA procedure

• Knee Society Score

  2 weeks after TKA procedure

Study Arms (2)

Methadone

EXPERIMENTAL

Patient will receive one perioperative dose of IV methadone prior to their surgical procedure in addition to standard of care medications.

Drug: Methadone

No medication

NO INTERVENTION

Patient will not receive only the standard of care medications for their procedure.

Interventions

Methadone DRUG

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

Methadone

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent from
• Stated willingness to comply with all study procedures and availability to attend all required visits for the duration of the study.
• Age 21- 75
• Unilateral total knee arthroplasty at Colorado Joint Replacement
• All individuals will be screened for drug use (opioid use, illicit drug use) at their preoperative appointment
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• AdventHealth: lead

Related Publications (7)

• Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.

  PMID: 21173206 BACKGROUND

• 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.

  PMID: 29847382 BACKGROUND

• 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.

  PMID: 37638083 BACKGROUND

• 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.

  PMID: 25911660 BACKGROUND

• 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.

  PMID: 25694266 BACKGROUND

• 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.

  PMID: 28887020 BACKGROUND

• 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.

  PMID: 33036845 BACKGROUND

MeSH Terms

Conditions

Agnosia

Interventions

Methadone

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Central Study Contacts

Makenna Hemmerle

CONTACT

303-260-2951; makenna.hemmerle@adventhealth.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: March 20, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share