Single-dose IV methadone during knee replacement to lower pain and opioid use

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

Phase 3 Interventional Medical University of South Carolina · NCT07226076

This trial will test whether one intraoperative IV dose of methadone reduces pain and the need for opioid pain pills after elective total knee replacement in adults.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment162 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorMedical University of South Carolina Academic / other
Locations1 site (Charleston, South Carolina)
Trial IDNCT07226076 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 3 trial enrolling adults having elective primary total knee arthroplasty under spinal anesthesia with mepivacaine. Participants receive a single intraoperative IV dose of methadone (0.15 mg/kg based on ideal body weight) or placebo, with standard perioperative care otherwise. The study measures acute postoperative pain levels and total opioid consumption after surgery. The trial is conducted at the Medical University of South Carolina and is limited to English-speaking participants able to provide written consent.

Who should consider this trial

Good fit: Adults aged 18 to 75 scheduled for elective primary total knee arthroplasty under spinal anesthesia with mepivacaine who can provide written informed consent and speak English are ideal candidates.

Not a fit: Patients with methadone or mepivacaine allergy, severe liver disease (Child-Pugh C), end-stage renal disease on dialysis, known prolonged QT syndrome, pregnant individuals, or those receiving nonspinal anesthesia are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, a single intraoperative methadone dose could reduce acute postoperative pain and lower the amount of opioid medication patients need after knee replacement.

How similar studies have performed: Prior randomized and observational studies in various surgical populations, including some joint replacement reports, have suggested intraoperative methadone can reduce postoperative pain and opioid use, but large confirmatory Phase 3 data are limited.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Charleston, South Carolina

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Post Operative Painpost-operative pain
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.