Postoperative PainPhase 3MELODYNCT07565870
Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery (MELODY)
A Phase 3 study testing Intravenous Methadone and Short-acting Opioids Intraoperative analgesia in people with Postoperative Pain and Recovery, run by Alexandre P. Joosten at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Pain, Recovery
- What is being tested?
- Intravenous Methadone and Short-acting Opioids Intraoperative analgesia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2026to 30 Mar 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
UCI
Irvine, California, 92697
SEAN COECKELENBERGH, MD PhD, +19496788922, scoeckel@hs.uci.edu
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Postoperative Pain, Recovery
- Being tested
- Intravenous Methadone, Short-acting Opioids Intraoperative analgesia
- Keywords
- Methadone, QoR-15, Quality of Recovery, Multimodal Analgesia, General Anesthesia
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous MethadoneDrug
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 analgesiaDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Short-acting Opioids Intraoperative analgesia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Postoperative Day 1 (24 hours after surgery)
Secondary outcomes (6)
QoR-15 score on postoperative day 2
Measured: Time Frame: Postoperative Day 2
Cumulative opioid consumption (MME)
Measured: Time Frame: 0-24 hours and 24-48 hours postoperatively
Maximum pain scores (Numeric Rating Scale)
Measured: Time Frame: Postoperative day 1 and 2
Opioid-free days
Measured: Time Frame: Within 7 days postoperatively
Opioid-related adverse events
Includes nausea, vomiting, sedation, respiratory depression
Measured: Time Frame: Up to 48 hours postoperatively
Health-related quality of life (EQ-5D-5L)
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.
Measured: 30 days post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2026
- Study start1 Jul 2026 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, parralle-group, superiority study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alexandre P. Joosten
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alexandre P. Joosten, University of California, Los Angeles
- Investigators
- Joseph Szokol, MD PhD, Study director, University of California, Los AngelesEVAN KARASCH, MD PhD, Study director, DUKE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07565870
- Sponsor's protocol ID
- IRB-25-2394
- Acronym
- MELODY
- Status last verified
- Apr 2026
- First submitted
- 23 Apr 2026
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: we will decide later
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery: A Multicentre Randomized Controlled Trial (MELODY Trial)
- ClinicalTrials.gov ID
- NCT07565870
- Acronym / sponsor ID
- MELODY / IRB-25-2394
- Conditions
- Postoperative Pain, Recovery
- Keywords
- Methadone, QoR-15, Quality of Recovery, Multimodal Analgesia, General Anesthesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Alexandre P. JoostenUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Mar 2027 (estimated)
- First posted
- 4 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- randomized, parralle-group, superiority study
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm: Methadone-Based Anesthesia | Experimental | Drug: Intravenous MethadoneIntervention: 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 Arm: Standard Opioid-Based Anesthesia | Active comparator | Drug: Short-acting Opioids Intraoperative analgesiaIntervention: Drug: Short-acting opioids Fentanyl and/or hydromorphone administered intraoperatively according to clinician judgment Reflects usual care practice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous MethadoneIntervention 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. | Drug | Experimental Arm: Methadone-Based Anesthesia |
| Short-acting Opioids Intraoperative analgesiantervention 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. | Drug | Active Comparator Arm: Standard Opioid-Based Anesthesia |
Primary outcome
Quality of Recovery (QoR-15) score on postoperative day 1
Time frame: 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.
6 secondary outcomes
QoR-15 score on postoperative day 2
Time frame: Time Frame: Postoperative Day 2
Cumulative opioid consumption (MME)
Time frame: Time Frame: 0-24 hours and 24-48 hours postoperatively
Maximum pain scores (Numeric Rating Scale)
Time frame: Time Frame: Postoperative day 1 and 2
Opioid-free days
Time frame: Time Frame: Within 7 days postoperatively
Opioid-related adverse events
Time frame: Time Frame: Up to 48 hours postoperatively
Health-related quality of life (EQ-5D-5L)
Time frame: 30 days post-surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Individual participant dataSharing planned: Undecided. we will decide later
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joseph Szokol, MD PhD study director
University of California, Los Angeles
EVAN KARASCH, MD PhD study director
DUKE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous Methadone and Short-acting Opioids Intraoperative analgesia in people with Postoperative Pain and Recovery, run by Alexandre P. Joosten at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact alexandre JOOSTEN, MD PhD (+13109627337, AJOOSTEN@MEDNET.UCLA.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quality of Recovery (QoR-15) score on postoperative day 1 (time frame: Postoperative Day 1 (24 hours after surgery)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.