Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study

NCT07222072 | Recruiting Phase 4 FDA Drug

• 1 other identifier: The MEND Study pilot
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a randomized, triple-blinded (patients, investigators, outcomes assessors), placebo-controlled pilot feasibility trial (Methadone to End Narcotic Dependence, MEND trial) to assess the feasibility and safety of postoperative oral methadone in patients undergoing spine surgery and collect preliminary data to inform a larger clinical trial that will test the opioid-sparing effects of methadone at 3 months after spine surgery.

Conditions

Post Operative Pain; Spinal Surgery

Keywords

Methadone; non-opioid; spinal surgery

Outcome Measures

Primary Outcomes (5)

• Feasibility and Acceptability-Participant Willingness/Recruitment

  Willingness of participants to be randomized Indicates acceptability of randomization among eligible patients Outcome Measure: % of eligible patient consenting to randomization

  7 days

• Feasibility and Acceptability-Provider Engagement

  Feasibility, acceptability and execution of clinical protocol based on the use of intraoperative IV methadone followed by a postoperative oral methadone regimen following spine surgery will be assessed by yes/no response to the following: Willingness of neurosurgeons/anesthesiologists to buy in to the trial Reflects institutional buy-in and clinical integration potential Outcome Measure: % of surgeons permitting patient enrollment and supporting protocol adherence

  7 days

• Feasibility and Execution-Protocol Compliance and Execution

  Feasibility of clinical protocol based on the use of intraoperative IV methadone followed by a postoperative oral methadone regimen following spine surgery will be assessed by yes/no response to the following: Compliance with the protocol, including specific study related procedures and timepoints specific to medication administration, adverse event reporting and data collection. Demonstrates deliverability and data reliability Outcome Measure: % adherence to all major protocol steps (drug administration, ECGs, AE reporting, opioid data)

  7 days

• Acceptability and Execution-Baseline Stratification Data

  Outcome Measure: % of enrolled patients with prior chronic opioid use

  18 months

• Feasibility and Execution-Follow-Up Completion

  Ability to assess primary endpoint (opioid use at 3 months).Measured by response rates to the telephone survey at 3 months

  90 days

Secondary Outcomes (3)

• Execution-Collection of Cardiac Rhythm Abnormalities

  18 months

• Execution-Collection of Respiratory Adverse Events

  18 months

• Estimate Reduction in Opioid Use

  90 days

Other Outcomes (1)

• Development of and effective study design

  24 months

Study Arms (2)

Methadone Group

ACTIVE COMPARATOR

Patients randomized to receive post operative methadone

Drug: Methadone

Patients randomized to receive (blinded) placebo

PLACEBO COMPARATOR

Patients will receive post operative placebo

Drug: Placebo

Interventions

Placebo DRUG

Patients randomized to receive (blinded) placebo will receive placebo 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.

Also known as: Placebo (Blinded) Group

Patients randomized to receive (blinded) placebo

Methadone DRUG

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.

Also known as: Methadone (Blinded) Group

Methadone Group

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥ 18 years of age
• Scheduled for multilevel lumbar and/or thoracic spine fusion (primary or revision)

You may not qualify if:

• \<18 or \>72 Years of age
• Body Mass Index \>40
• Known allergy to methadone
• Pregnant females
• Non-English-speaking patients

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Related Publications (27)

• Berardino K, Carroll AH, Kaneb A, Civilette MD, Sherman WF, Kaye AD. An Update on Postoperative Opioid Use and Alternative Pain Control Following Spine Surgery. Orthop Rev (Pavia). 2021 Jun 22;13(2):24978. doi: 10.52965/001c.24978. eCollection 2021.

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• Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, Bohnert ASB, Kheterpal S, Nallamothu BK. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017 Jun 21;152(6):e170504. doi: 10.1001/jamasurg.2017.0504. Epub 2017 Jun 21.

  PMID: 28403427 BACKGROUND

• 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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• Martin BI, Turner JA, Mirza SK, Lee MJ, Comstock BA, Deyo RA. Trends in health care expenditures, utilization, and health status among US adults with spine problems, 1997-2006. Spine (Phila Pa 1976). 2009 Sep 1;34(19):2077-84. doi: 10.1097/BRS.0b013e3181b1fad1.

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• Luby AO, Alessio-Bilowus D, Hu HM, Brummett CM, Waljee JF, Bicket MC. Trends in Opioid Prescribing and New Persistent Opioid Use After Surgery in the United States. Ann Surg. 2025 Mar 1;281(3):347-352. doi: 10.1097/SLA.0000000000006461. Epub 2024 Aug 1.

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MeSH Terms

Conditions

Pain, Postoperative

Interventions

Methadone; Population Groups

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Demography; Population Characteristics

Study Officials

• Shobana Rajan, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Andra Duncan, MD

  The Cleveland Clinic

  STUDY CHAIR

Central Study Contacts

Stephanie Stoianoff, MBA

CONTACT

12164440231; stoians@ccf.org

Sandra Durbin, CLPN, CCRP

CONTACT

216-269-4073; durbins@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized 1:1 to postoperative methadone versus placebo on arrival to the operating room. Randomization will occur using a computer-generated randomization system in REDCap, with the sequence of randomly sized blocks pre-determined using the PLAN Procedure in SAS statistical software, stratified by previous history of opioid use (Opioid naïve versus those taking opioids before surgery).
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2025
• First Posted: October 29, 2025
• Study Start: November 15, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: De-identified data will be available post-analysis in abstract/journal articles.

Locations

US (1)