Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery: A Multicentre Randomized Controlled Trial (MELODY Trial)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Quality of Recovery (QoR-15) score on postoperative day 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Intravenous Methadone (Drug)
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
干预措施: Short-acting Opioids Intraoperative analgesia (Drug)
结局指标
主要结局
Quality of Recovery (QoR-15) score on postoperative day 1
时间窗: 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.
次要结局
- Maximum pain scores (Numeric Rating Scale)(Time Frame: Postoperative day 1 and 2)
- 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)
- Opioid-free days(Time Frame: Within 7 days postoperatively)
- Opioid-related adverse events(Time Frame: Up to 48 hours postoperatively)
- Health-related quality of life (EQ-5D-5L)(30 days post-surgery)
研究者
Alexandre P. Joosten
PI
University of California, Los Angeles