[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07565870":3,"trial-entities:NCT07565870":125,"trial-summary:NCT07565870":129},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":21,"study_type":27,"primary_purpose":28,"phases":29,"enrollment_info":31,"interventions":34,"primary_outcomes":46,"secondary_outcomes":51,"sex":72,"minimum_age":73,"maximum_age":74,"healthy_volunteers":15,"eligibility_criteria":75,"std_ages":91,"locations":94,"central_contacts":110,"overall_officials":115,"references":123,"see_also_links":124},"NCT07565870","IRB-25-2394","Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery (MELODY)","Methadone for Enhanced Postoperative Analgesia in Intermediate-Risk Noncardiac Surgery: A Multicentre Randomized Controlled Trial (MELODY Trial)","NOT_YET_RECRUITING","2027-03-30","2026-04","2026-05-04","2026-07-01","Alexandre P. Joosten","OTHER",false,"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.\n\nMethadone 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.\n\nThe 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.","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.\n\nMethadone 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.\n\nThe 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.\n\nAll 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.",[19,20],"Postoperative Pain","Recovery",[22,23,24,25,26],"Methadone","QoR-15","Quality of Recovery","Multimodal Analgesia","General Anesthesia","INTERVENTIONAL","TREATMENT",[30],"PHASE3",{"count":32,"type":33},400,"ESTIMATED",[35,41],{"type":36,"name":37,"description":38,"armGroupLabels":39},"DRUG","Intravenous Methadone","Intervention Description - Intravenous Methadone\n\nA single intravenous dose of methadone (0.25 mg\u002Fkg 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.",[40],"Experimental Arm: Methadone-Based Anesthesia",{"type":36,"name":42,"description":43,"armGroupLabels":44},"Short-acting Opioids Intraoperative analgesia","ntervention Description - Short-acting Opioids\n\nIntraoperative analgesia using short-acting opioids (e.g., fentanyl and\u002For 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.",[45],"Active Comparator Arm: Standard Opioid-Based Anesthesia",[47],{"measure":48,"description":49,"timeFrame":50},"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.","Postoperative Day 1 (24 hours after surgery)",[52,55,58,61,64,68],{"measure":53,"timeFrame":54},"QoR-15 score on postoperative day 2","Time Frame: Postoperative Day 2",{"measure":56,"timeFrame":57},"Cumulative opioid consumption (MME)","Time Frame: 0-24 hours and 24-48 hours postoperatively",{"measure":59,"timeFrame":60},"Maximum pain scores (Numeric Rating Scale)","Time Frame: Postoperative day 1 and 2",{"measure":62,"timeFrame":63},"Opioid-free days","Time Frame: Within 7 days postoperatively",{"measure":65,"description":66,"timeFrame":67},"Opioid-related adverse events","Includes nausea, vomiting, sedation, respiratory depression","Time Frame: Up to 48 hours postoperatively",{"measure":69,"description":70,"timeFrame":71},"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:\n\nMobility: 1 = No problems, 5 = Extreme problems Self-care: 1 = No problems, 5 = Extreme problems Usual activities: 1 = No problems, 5 = Extreme problems Pain\u002Fdiscomfort: 1 = No problems, 5 = Extreme problems Anxiety\u002Fdepression: 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","ALL","18 Years",null,{"inclusion":76,"exclusion":82,"raw_text":90},[77,78,79,80,81],"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",[83,84,85,86,87,88,89],"Severe hepatic dysfunction (Child-Pugh C)","Severe renal impairment (eGFR \\\u003C30 mL\u002Fmin\u002F1.73 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","Inclusion Criteria\n\n* Age ≥18 years\n* Elective intermediate-risk noncardiac surgery under general anesthesia\n* ASA physical status I-III\n* Expected hospital stay ≥24 hours\n* Ability to provide informed consent\n\nExclusion Criteria\n\n* Severe hepatic dysfunction (Child-Pugh C)\n* Severe renal impairment (eGFR \\\u003C30 mL\u002Fmin\u002F1.73 m²)\n* Known allergy to methadone or opioids\n* Pregnancy or breastfeeding\n* Chronic opioid use or opioid use disorder\n* Planned use of epidural or regional analgesia\n* Inability to complete study assessments",[92,93],"ADULT","OLDER_ADULT",[95],{"facility":96,"city":97,"state":98,"zip":99,"country":100,"contacts":101,"geoPoint":107},"UCI","Irvine","California","92697","United States",[102],{"name":103,"role":104,"phone":105,"email":106},"SEAN COECKELENBERGH, MD PhD","CONTACT","+19496788922","scoeckel@hs.uci.edu",{"lat":108,"lon":109},33.66946,-117.82311,[111],{"name":112,"role":104,"phone":113,"email":114},"alexandre JOOSTEN, MD PhD","+13109627337","AJOOSTEN@MEDNET.UCLA.EDU",[116,120],{"name":117,"affiliation":118,"role":119},"Joseph Szokol, MD PhD","University of California, Los Angeles","STUDY_DIRECTOR",{"name":121,"affiliation":122,"role":119},"EVAN KARASCH, MD PhD","DUKE",[],[],{"nct_id":4,"conditions":126,"biomarkers":128},[127],"Post-Operative Pain",[],{"nct_id":4,"found":130,"summary":131,"prompt_version":141},true,{"design":132,"status":133,"heading":134,"summary":135,"follow_up":136,"word_count":137,"commitments":138,"compensation":139,"drugs_mentioned":140},"This is a randomized study where 400 participants will be assigned by chance to receive either IV methadone or standard short-acting opioids during surgery.","completed","MELODY Trial: Methadone for Postoperative Pain Relief","This study, called MELODY, is looking at whether a single dose of intravenous (IV) methadone given during surgery can help reduce pain and improve recovery after noncardiac surgery. Currently, many patients still experience significant pain after surgery, and this study aims to see if methadone, which works differently than common short-acting pain medications, can provide longer-lasting pain relief. You might be able to join if you are an adult having elective intermediate-risk noncardiac surgery, are generally healthy (ASA physical status I-III), and expect to stay in the hospital for at least 24 hours. The main goal is to see how well you recover on the first day after surgery, measured by a special questionnaire called QoR-15. The study's current status is unclear.","Your recovery will be assessed on postoperative day 1 (24 hours after surgery).",122,"You would receive either IV methadone or short-acting opioids during your surgery. Your recovery will be assessed on the first day after surgery using a questionnaire.","Not stated in the trial record.",[],"v2"]