Methadone for Postoperative Pain

(MELODY Trial)

Overseen By alexandre JOOSTEN, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexandre P. Joosten

Must not be taking: Opioids

Disqualifiers: Severe hepatic dysfunction, severe renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Intraoperative

What You Need to Know Before You Apply

What is the purpose of this trial?

Postoperative pain control remains suboptimal for a large proportion of surgical patients and is frequently associated with slower recovery and higher reliance on opioids after surgery. Current intraoperative analgesic approaches predominantly use short-acting opioids, whose rapid pharmacokinetics can lead to variable drug exposure and inconsistent control of nociceptive stimuli.

Methadone has a different pharmacologic profile, combining prolonged μ-opioid receptor activity with N-methyl-D-aspartate receptor antagonism, allowing sustained analgesia following a single intraoperative administration and potentially enhancing postoperative recovery.

The MELODY trial is a multicentre, randomized, patient-blinded clinical study designed to compare a single intravenous dose of methadone given at induction with conventional short-acting opioid-based anesthesia in adults undergoing intermediate-risk noncardiac surgery. The primary aim is to evaluate whether this strategy leads to improved quality of recovery on the first postoperative day.

Who Is on the Research Team?

Joseph Szokol, MD PhD

Principal Investigator

University of California, Los Angeles

EVAN KARASCH, MD PhD

Principal Investigator

DUKE

Are You a Good Fit for This Trial?

Inclusion Criteria

I am 18 years old or older.

Ability to provide informed consent

ASA physical status I-III

Exclusion Criteria

Chronic opioid use or opioid use disorder

I am unable to complete the required study assessments.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either intravenous methadone at induction or standard short-acting opioid-based anesthesia during surgery

Intraoperative

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for quality of recovery and opioid-related adverse events

48 hours

Continuous monitoring

Follow-up

Participants' health-related quality of life is assessed using EQ-5D-5L

30 days post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

How Is the Trial Designed?

Group I: Experimental Arm: Methadone-Based Anesthesia Experimental Treatment 1 Intervention

Intervention: Drug: Methadone Intravenous methadone 0.25 mg/kg (ideal body weight) administered at induction Optional supplemental dose (2 mg) at emergence if clinically indicated Additional intraoperative short-acting opioids discouraged

Group II: Active Comparator Arm: Standard Opioid-Based Anesthesia Active Control 1 Intervention

Intervention: Drug: Short-acting opioids Fentanyl and/or hydromorphone administered intraoperatively according to clinician judgment Reflects usual care practice

Who Is Running the Clinical Trial?

Alexandre P. Joosten

Lead Sponsor