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.
研究概览
详细说明
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.
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名：alexandre JOOSTEN, MD PhD
- 电话号码：+13109627337
- 邮箱：AJOOSTEN@MEDNET.UCLA.EDU
学习地点
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California
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Irvine、California、美国、92697
- UCI
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接触：
- SEAN COECKELENBERGH, MD PhD
- 电话号码：+19496788922
- 邮箱：scoeckel@hs.uci.edu
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：单身的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：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. |
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有源比较器：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. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Quality of Recovery (QoR-15) score on postoperative day 1
大体时间：Postoperative Day 1 (24 hours after surgery)
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Quality of recovery assessed using the validated 15-item QoR-15 questionnaire.
Scores range from 0 to 150, with higher scores indicating better recovery.
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Postoperative Day 1 (24 hours after surgery)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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QoR-15 score on postoperative day 2
大体时间：Time Frame: Postoperative Day 2
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Time Frame: Postoperative Day 2
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Cumulative opioid consumption (MME)
大体时间：Time Frame: 0-24 hours and 24-48 hours postoperatively
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Time Frame: 0-24 hours and 24-48 hours postoperatively
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Maximum pain scores (Numeric Rating Scale)
大体时间：Time Frame: Postoperative day 1 and 2
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Time Frame: Postoperative day 1 and 2
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Opioid-free days
大体时间：Time Frame: Within 7 days postoperatively
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Time Frame: Within 7 days postoperatively
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Opioid-related adverse events
大体时间：Time Frame: Up to 48 hours postoperatively
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Includes nausea, vomiting, sedation, respiratory depression
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Time Frame: Up to 48 hours postoperatively
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Health-related quality of life (EQ-5D-5L)
大体时间：30 days post-surgery
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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
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合作者和调查者
调查人员
- 研究主任：Joseph Szokol, MD PhD、University of California, Los Angeles
- 研究主任：EVAN KARASCH, MD PhD、Duke
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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