Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study
NCT ID: NCT07222072
Last Updated: 2025-11-12
Study Results
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Basic Information
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RECRUITING
PHASE4
120 participants
INTERVENTIONAL
2025-11-03
2028-10-31
Brief Summary
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Detailed Description
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Patients undergoing spine surgery experience severe postoperative back pain immediately after surgery, which requires treatment with potent opioid medications. Severe pain in the first 1 to 3 days after surgery often develops into chronic back pain, which increases risk for long-term use and abuse of prescription opioid drugs. Importantly, compared with all other surgical procedures, back and spine surgery is associated with the highest risk of long-term use and abuse of prescription opioid medications. Certainly, chronic back pain requires opioid use in approximately 50% of patients at three months after surgery, 40% at six months, 30% at one year, and 17% at two years. A financial burden exists as well. Over the past 10 years, annual prescription opioid expenditures for pain after spine-related surgery increased 660% from $246 million in 1997 to $1.9 billion in 2006. Monthly direct and indirect costs associated with the treatment of postoperative persistent and chronic back pain totaled an average US $3,455 per patient. These data indicate that new approaches that provide effective, long-lasting, and safe treatment of postoperative pain after complex spine surgery while reducing risk of persistent and chronic postoperative pain and prolonged opioid use and reducing cost are needed.
Multiple randomized clinical trials in patients undergoing a variety of surgical procedures have demonstrated that intraoperative methadone significantly reduces postoperative analgesic requirements in the immediate postoperative period, compared to shorter-acting opioids. Methadone is a unique long-acting opioid medication that demonstrates rapid onset and prolonged duration of action with a half-life of 24-36 hours and pain relief lasting 8-12 hours. Like other opioids, methadone activates the mu-opioid receptor, but it also has additional effects on the brain, such as blocking NMDA receptors and reducing reuptake of serotonin and norepinephrine. These actions may help improve recovery by reducing pain sensitivity, preventing tolerance to the medication with euphoric effects, preventing opioid-induced hyperalgesia and opioid tolerance. One investigation studied the impact of methadone on persistent and chronic post-surgical pain in a small randomized controlled trial (RCT) with 66 patients. Participants were randomized to receive either a single intraoperative intravenous dose of methadone (0.2 mg/kg) or intravenous hydromorphone (2 mg). Methadone not only reduced the incidence of post-surgical pain in the study group. but also the percentage of patients who required opioid analgesics at three months (10 versus 41%), suggesting a protective effect against prolonged opioid consumption. Pilot data from another investigation using preoperative oral methadone in patients undergoing cardiac surgery showed reduction in postoperative morphine consumption in the first 24 hours. If acute postoperative pain is reduced, the development of chronic pain may also decrease, as well as the need for long-term opioid therapy, dependence, and abuse.
Although methadone provides effective analgesia for major surgery, a thorough safety assessment of perioperative intravenous methadone is needed. A large retrospective study of 1,478 patients after major spine fusion surgery who received IV methadone (0.13 mg/kg) along with other analgesics, including lidocaine, ketamine, and hydromorphone noted respiratory depression in one-third of patients and hypoxia in nearly 80%. Other concerns include a nearly 60% incidence of electrocardiographic QTc prolongation and 1.1% experienced myocardial infarction (MI) postoperatively. However, there is limited data on the impact of a single perioperative dose of methadone on QTc prolongation. Additional potential complications such as respiratory depression requires further investigation.
If proven safe and effective, postoperative pain therapy with methadone could offer a simple, practical strategy to improve long-term outcomes in this high-risk population undergoing spine surgery. This investigation will the safety and efficacy of postoperative methadone treatment in patients undergoing spine surgery and the opioid-sparing effects of methadone at 3 months after surgery.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
OTHER
QUADRUPLE
Study Groups
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Patients randomized to receive (blinded) methadone.
Methadone group: Patients randomized to receive (blinded) methadone will receive methadone 5 mg twice daily on postoperative days 1 and 2 followed by 5 mg daily on postoperative days 3, 4, and 5. Patients taking preoperative opioids will be able to return to their baseline opioids immediately after surgery
Methadone
Patients randomized to receive (blinded) methadone: 5 mg twice daily on postoperative (post-op) days 1 and 2 followed by 5 mg daily on postop days 3, 4, and 5. Patients taking preoperative opioids will return to their baseline opioid schedule after surgery. Postop oral methadone is initiated on postop day 1 as a layered continuation of intraoperative analgesia. However, in patients who receive continuous methadone therapy (similar to methadone patients enrolled in our trial), oral administration every 12 hours is effective.
Patients randomized to receive (blinded) placebo will receive placebo tablets twice daily on day 1 and day 2 and once daily on day 3, 4 and 5. Patients taking preoperative opioids will return to baseline opioid schedule after surgery.
Patients randomized to receive (blinded) placebo
Patients randomized to receive (blinded) placebo will receive placebo tablets twice daily on day 1 and day 2 and once daily on day 3, 4 and 5. Patients taking preoperative opioids will return to their baseline opioid schedule after surgery.
Placebo
Patients randomized to receive (blinded) placebo will receive placebo tablets twice daily on day 1 and day 2 and once daily on day 3, 4 and 5. Patients taking preoperative opioids will return to baseline opioid schedule after surgery.
Interventions
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Methadone
Patients randomized to receive (blinded) methadone: 5 mg twice daily on postoperative (post-op) days 1 and 2 followed by 5 mg daily on postop days 3, 4, and 5. Patients taking preoperative opioids will return to their baseline opioid schedule after surgery. Postop oral methadone is initiated on postop day 1 as a layered continuation of intraoperative analgesia. However, in patients who receive continuous methadone therapy (similar to methadone patients enrolled in our trial), oral administration every 12 hours is effective.
Patients randomized to receive (blinded) placebo will receive placebo tablets twice daily on day 1 and day 2 and once daily on day 3, 4 and 5. Patients taking preoperative opioids will return to baseline opioid schedule after surgery.
Placebo
Patients randomized to receive (blinded) placebo will receive placebo tablets twice daily on day 1 and day 2 and once daily on day 3, 4 and 5. Patients taking preoperative opioids will return to baseline opioid schedule after surgery.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Scheduled for multilevel lumbar and/or thoracic spine fusion (primary or revision)
Exclusion Criteria
* Body Mass Indes \>40
* Known allergy to methadone
* Pregnant females
* Non-English-speaking patients
18 Years
70 Years
ALL
No
Sponsors
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The Cleveland Clinic
OTHER
Responsible Party
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Principal Investigators
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Shobana Rajan, MD
Role: PRINCIPAL_INVESTIGATOR
The Cleveland Clinic
Andra Duncan, MD
Role: STUDY_CHAIR
The Cleveland Clinic
Locations
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Cleveland Clinic
Cleveland, Ohio, United States
Countries
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Central Contacts
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Facility Contacts
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Stephanie Stoianoff, MBA
Role: primary
Sandra Durbin, CLPN, CCRP
Role: backup
References
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Dunn LK, Yerra S, Fang S, Hanak MF, Leibowitz MK, Alpert SB, Tsang S, Durieux ME, Nemergut EC, Naik BI. Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients. J Opioid Manag. 2018 Mar/Apr;14(2):83-87. doi: 10.5055/jom.2018.0435.
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Other Identifiers
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The MEND Study pilot
Identifier Type: -
Identifier Source: org_study_id