Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery (MELODY)

NCT07565870 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: IRB-25-2394
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Pain; Recovery

Keywords

Methadone; QoR-15; Quality of Recovery; Multimodal Analgesia; General Anesthesia

Outcome Measures

Primary Outcomes (1)

• Quality of Recovery (QoR-15) score on postoperative day 1

  Quality of recovery assessed using the validated 15-item QoR-15 questionnaire. Scores range from 0 to 150, with higher scores indicating better recovery.

  Postoperative Day 1 (24 hours after surgery)

Secondary Outcomes (6)

• QoR-15 score on postoperative day 2

  Time Frame: Postoperative Day 2

• Cumulative opioid consumption (MME)

  Time Frame: 0-24 hours and 24-48 hours postoperatively

• Maximum pain scores (Numeric Rating Scale)

  Time Frame: Postoperative day 1 and 2

• Opioid-free days

  Time Frame: Within 7 days postoperatively

• Opioid-related adverse events

  Time Frame: Up to 48 hours postoperatively

Study Arms (2)

Experimental Arm: Methadone-Based Anesthesia

EXPERIMENTAL

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

Drug: Intravenous Methadone

Active Comparator Arm: Standard Opioid-Based Anesthesia

ACTIVE COMPARATOR

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

Drug: Short-acting Opioids Intraoperative analgesia

Interventions

Intravenous Methadone DRUG

Intervention Description - Intravenous Methadone A single intravenous dose of methadone (0.25 mg/kg based on ideal body weight) administered at induction of anesthesia to provide sustained intraoperative and early postoperative analgesia. Additional short-acting opioids are discouraged but may be administered if clinically required. A supplemental dose of methadone (2 mg) may be given at emergence in case of significant nociceptive signs.

Experimental Arm: Methadone-Based Anesthesia

Short-acting Opioids Intraoperative analgesia DRUG

ntervention Description - Short-acting Opioids Intraoperative analgesia using short-acting opioids (e.g., fentanyl and/or hydromorphone) administered at induction and throughout surgery according to clinician judgment and institutional practice. This approach reflects usual care, with dosing and timing determined pragmatically based on intraoperative needs.

Active Comparator Arm: Standard Opioid-Based Anesthesia

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Elective intermediate-risk noncardiac surgery under general anesthesia
• ASA physical status I-III
• Expected hospital stay ≥24 hours
• Ability to provide informed consent

You may not qualify if:

• Severe hepatic dysfunction (Child-Pugh C)
• Severe renal impairment (eGFR \<30 mL/min/1.73 m²)
• Known allergy to methadone or opioids
• Pregnancy or breastfeeding
• Chronic opioid use or opioid use disorder
• Planned use of epidural or regional analgesia
• Inability to complete study assessments

Sponsors & Collaborators

• Alexandre P. Joosten: lead

Study Sites (1)

UCI

Irvine, California, 92697, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Joseph Szokol, MD PhD

  University of California, Los Angeles

  STUDY DIRECTOR

• EVAN KARASCH, MD PhD

  DUKE

  STUDY DIRECTOR

Central Study Contacts

alexandre JOOSTEN, MD PhD

CONTACT

+13109627337; AJOOSTEN@MEDNET.UCLA.EDU

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded to treatment allocation. The intraoperative anesthesiologist cannot be blinded due to the nature of drug preparation and administration. Postoperative care providers, including PACU nurses and surgical teams, may have access to the anesthesia record and are therefore not blinded. Outcome assessment is based on patient-reported measures (QoR-15), which are collected without disclosure of group assignment. Data analysis will be conducted using de-identified datasets.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PI

Model Details: randomized, parralle-group, superiority study

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)