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

Conditions

• Postoperative Pain
• Recovery

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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.
• 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.

Study Details

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.

Key Dates

Start date

Jul 1, 2026

Status verified

Apr 2026

Primary completion

Dec 31, 2026

Completion

Mar 30, 2027

Study Design

Enrollment

400 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Experimental Arm: Methadone-Based Anesthesia
  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
• Active Comparator: Active Comparator Arm: Standard Opioid-Based Anesthesia
  Intervention: Drug: Short-acting opioids Fentanyl and/or hydromorphone administered intraoperatively according to clinician judgment Reflects usual care practice

Primary Outcome Measure

Quality of Recovery (QoR-15) score on postoperative day 1 [ Time Frame: Postoperative Day 1 (24 hours after surgery) ]

Central Contacts

• alexandre JOOSTEN, MD PhD
  +13109627337
  [email protected]

Locations (1)

Find similar trials in Irvine, CA

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