Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery (MELODY) (MELODY)
Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery: A Multicentre Randomized Controlled Trial (MELODY 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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Acute postoperative pain remains insufficiently controlled in a substantial proportion of surgical patients, with more than half reporting moderate-to-severe pain after surgery. Standard intraoperative opioid strategies rely on short-acting agents such as fentanyl or hydromorphone, which are associated with rapid clearance and fluctuating plasma concentrations that may contribute to variability in nociceptive control and increased postoperative opioid requirements.
Methadone offers a pharmacologic profile that may address these limitations. It provides prolonged analgesic effect due to its long elimination half-life, rapid effect-site equilibration, and additional N-methyl-D-aspartate receptor antagonism, potentially reducing central sensitization and improving postoperative pain control.
The MELODY trial is a multicentre, patient-blinded, randomized, parallel-group superiority trial conducted across University of California hospitals. Participants are randomized in a 1:1 ratio to receive either intravenous methadone at induction or standard short-acting opioid-based anesthesia.
All patients receive a standardized multimodal analgesic regimen to isolate the effect of the intraoperative opioid strategy. The primary outcome is quality of recovery on postoperative day 1, assessed using the validated Quality of Recovery-15 (QoR-15) questionnaire. Secondary outcomes include opioid consumption, pain scores, opioid-related adverse events, and health-related quality of life.
Studietype
Inschrijving (Geschat)
Fase
- Fase 3
Contacten en locaties
Studiecontact
- Naam: alexandre JOOSTEN, MD PhD
- Telefoonnummer: +13109627337
- E-mail: AJOOSTEN@MEDNET.UCLA.EDU
Studie Locaties
-
-
California
-
Irvine, California, Verenigde Staten, 92697
- UCI
-
Contact:
- SEAN COECKELENBERGH, MD PhD
- Telefoonnummer: +19496788922
- E-mail: scoeckel@hs.uci.edu
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Enkel
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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 |
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. |
|
Actieve vergelijker: 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 |
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. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Quality of Recovery (QoR-15) score on postoperative day 1
Tijdsspanne: Postoperative Day 1 (24 hours after surgery)
|
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)
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
QoR-15 score on postoperative day 2
Tijdsspanne: Time Frame: Postoperative Day 2
|
Time Frame: Postoperative Day 2
|
|
|
Cumulative opioid consumption (MME)
Tijdsspanne: Time Frame: 0-24 hours and 24-48 hours postoperatively
|
Time Frame: 0-24 hours and 24-48 hours postoperatively
|
|
|
Maximum pain scores (Numeric Rating Scale)
Tijdsspanne: Time Frame: Postoperative day 1 and 2
|
Time Frame: Postoperative day 1 and 2
|
|
|
Opioid-free days
Tijdsspanne: Time Frame: Within 7 days postoperatively
|
Time Frame: Within 7 days postoperatively
|
|
|
Opioid-related adverse events
Tijdsspanne: Time Frame: Up to 48 hours postoperatively
|
Includes nausea, vomiting, sedation, respiratory depression
|
Time Frame: Up to 48 hours postoperatively
|
|
Health-related quality of life (EQ-5D-5L)
Tijdsspanne: 30 days post-surgery
|
The EQ-5D-5L (EuroQol 5-Dimension 5-Level Version) is a health-related quality of life assessment tool that measures quality of life across five dimensions: Mobility: 1 = No problems, 5 = Extreme problems Self-care: 1 = No problems, 5 = Extreme problems Usual activities: 1 = No problems, 5 = Extreme problems Pain/discomfort: 1 = No problems, 5 = Extreme problems Anxiety/depression: 1 = Not at all, 5 = Extremely severe Each dimension is scored on a 5-level scale, allowing for a detailed assessment of health status. |
30 days post-surgery
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Joseph Szokol, MD PhD, University of California, Los Angeles
- Studie directeur: EVAN KARASCH, MD PhD, Duke
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- IRB-25-2394
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .