Post Operative PainPhase 4MENDNCT07222072
Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study
A Phase 4 study testing Methadone in people with Post Operative Pain and Spinal Surgery, run by The Cleveland Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 72 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Operative Pain, Spinal Surgery
- What is being tested?
- Methadone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2025to Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult ≥ 18 years of age
- Scheduled for multilevel lumbar and/or thoracic spine fusion (primary or revision)
Who cannot join
- <18 or >72 Years of age
- Body Mass Index >40
- Known allergy to methadone
- Pregnant females
- Non-English-speaking patients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Stephanie Stoianoff, MBA, 216-444-0231, stoians@ccf.org
Sandra Durbin, CLPN, CCRP, durbins@ccf.org
About this study
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.
Read the detailed description
The Centers for Disease Control and Prevention reports a nearly 10-fold increase in the number of deaths from all types of drug overdose over the past 20 years, including 82,000 deaths that occurred in 2022 alone. Prescription opioid medications contribute to drug overdose deaths. In fact, nearly 294,000 people in the US died from a drug overdose involving prescription opioid medications between 1999 and 2022 - a 4-fold increase in prescription drug overdose deaths. Surgery is often the first exposure to opioid medications for many patients. Severe pain after surgery requires potent opioid medications which control pain but includes risk of long-term opioid-dependence. Long-term opioid use and abuse may lead to opioid addiction, overdose and even death.
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
- Post Operative Pain, Spinal Surgery
- Being tested
- Methadone, Placebo
- Keywords
- Methadone, non-opioid, spinal surgery
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Also called Methadone (Blinded) Group
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.
PlaceboDrug
Also called Placebo (Blinded) Group
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.
| Study group | Role | What they receive |
|---|---|---|
| Methadone Group | Active comparator | Patients randomized to receive post operative methadone Receives: Drug: Methadone |
| Patients randomized to receive (blinded) placebo | Placebo comparator | Patients will receive post operative placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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)
Measured: 7 days
Acceptability and Execution-Baseline Stratification Data
Outcome Measure: % of enrolled patients with prior chronic opioid use
Measured: 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
Measured: 90 days
Secondary outcomes (3)
Execution-Collection of Cardiac Rhythm Abnormalities
- ECG collected on postoperative days 1, 2 and 3. Presence of cardiac arrhythmias (frequent premature ventricular contractions, ventricular arrhythmias) requiring treatment will be collected. An increase in QTc interval >500 ms or >25% from baseline will be compared to baseline ECG,
Measured: 18 months
Execution-Collection of Respiratory Adverse Events
Respiratory depression indicators will be measured every 6 hours.
- The presence of any of the following will be considered respiratory depression:
- Respiratory rate <8 or oxygen saturation <90% for longer than 5 minutes
- Increased oxygen requirement by ≥ 2 L O2 for 15 min
- naloxone use. Patients who are receiving
- supplemental oxygen
Measured: 18 months
Estimate Reduction in Opioid Use
To estimate reduction in opioid use (Morphine Milligram Equivalents, MME) in the acute postoperative period as a mechanistic indicator for decrease in opioid usage at 3 months.
Postoperative 5-day opioid requirements assessed by total MME (5 days duration or length of hospitalization, whichever is earlier) will be compared between methadone and placebo groups
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2025
- Study start15 Nov 2025
- Primary completionOct 2027 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Post Operative PainStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shobana Rajan, MD, Principal investigator, The Cleveland ClinicAndra Duncan, MD, Study chair, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07222072
- Sponsor's protocol ID
- The MEND Study pilot
- Acronym
- MEND
- Status last verified
- Dec 2025
- First submitted
- 21 Oct 2025
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigator plans to share information by presenting abstract/journal materials pending results.
Publications
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.
PubMed 34745473Brummett 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.
PubMed 28403427Dunn 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.
PubMed 29733094Martin 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.
PubMed 19675510Luby 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.
PubMed 39087325Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
PubMed 21173206Banks ML, Roma PG, Folk JE, Rice KC, Negus SS. Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis. Psychopharmacology (Berl). 2011 Aug;216(3):431-9. doi: 10.1007/s00213-011-2235-2. Epub 2011 Mar 3.
PubMed 21369752Davidson EM, Coggeshall RE, Carlton SM. Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport. 1997 Mar 3;8(4):941-6. doi: 10.1097/00001756-199703030-00025.
PubMed 9141069Stubhaug A, Breivik H. Long-term treatment of chronic neuropathic pain with the NMDA (N-methyl-D-aspartate) receptor antagonist ketamine. Acta Anaesthesiol Scand. 1997 Mar;41(3):329-31. doi: 10.1111/j.1399-6576.1997.tb04693.x. No abstract available.
PubMed 9113174Sotgiu ML, Valente M, Storchi R, Caramenti G, Biella GE. Cooperative N-methyl-D-aspartate (NMDA) receptor antagonism and mu-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain. Pharmacol Res. 2009 Oct;60(4):284-90. doi: 10.1016/j.phrs.2009.04.002. Epub 2009 Apr 11.
PubMed 19717013Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999 May;289(2):1048-53.
PubMed 10215686Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain. 1995 Sep;62(3):259-274. doi: 10.1016/0304-3959(95)00073-2.
PubMed 8657426Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.
PubMed 16508405Kreek MJ, Borg L, Ducat E, Ray B. Pharmacotherapy in the treatment of addiction: methadone. J Addict Dis. 2010 Apr;29(2):200-16. doi: 10.1080/10550881003684798.
PubMed 20407977Kreutzwiser D, Tawfic QA. Methadone for Pain Management: A Pharmacotherapeutic Review. CNS Drugs. 2020 Aug;34(8):827-839. doi: 10.1007/s40263-020-00743-3.
PubMed 32564328
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study
- ClinicalTrials.gov ID
- NCT07222072
- Acronym / sponsor ID
- MEND / The MEND Study pilot
- Conditions
- Post Operative Pain, Spinal Surgery
- Keywords
- Methadone, non-opioid, spinal surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 15 Nov 2025 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 29 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The Centers for Disease Control and Prevention reports a nearly 10-fold increase in the number of deaths from all types of drug overdose over the past 20 years, including 82,000 deaths that occurred in 2022 alone. Prescription opioid medications contribute to drug overdose deaths. In fact, nearly 294,000 people in the US died from a drug overdose involving prescription opioid medications between 1999 and 2022 - a 4-fold increase in prescription drug overdose deaths. Surgery is often the first exposure to opioid medications for many patients. Severe pain after surgery requires potent opioid medications which control pain but includes risk of long-term opioid-dependence. Long-term opioid use and abuse may lead to opioid addiction, overdose and even death.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methadone Group | Active comparator | Drug: MethadonePatients randomized to receive post operative methadone |
| Patients randomized to receive (blinded) placebo | Placebo comparator | Drug: PlaceboPatients will receive post operative placebo |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult ≥ 18 years of age
- Scheduled for multilevel lumbar and/or thoracic spine fusion (primary or revision)
Key exclusion criteria (5 listed)
- <18 or >72 Years of age
- Body Mass Index >40
- Known allergy to methadone
- Pregnant females
- Non-English-speaking patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneAlso: Methadone (Blinded) GroupPatients 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. | Drug | Methadone Group |
| PlaceboAlso: Placebo (Blinded) GroupPatients 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. | Drug | Patients randomized to receive (blinded) placebo |
Primary outcome
Feasibility and Acceptability-Participant Willingness/Recruitment
Time frame: 7 days
Willingness of participants to be randomized Indicates acceptability of randomization among eligible patients Outcome Measure: % of eligible patient consenting to randomization
Feasibility and Acceptability-Provider Engagement
Time frame: 7 days
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
Feasibility and Execution-Protocol Compliance and Execution
Time frame: 7 days
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)
Acceptability and Execution-Baseline Stratification Data
Time frame: 18 months
Outcome Measure: % of enrolled patients with prior chronic opioid use
Feasibility and Execution-Follow-Up Completion
Time frame: 90 days
Ability to assess primary endpoint (opioid use at 3 months).Measured by response rates to the telephone survey at 3 months
3 secondary outcomes
Execution-Collection of Cardiac Rhythm Abnormalities
Time frame: 18 months
Execution-Collection of Respiratory Adverse Events
Time frame: 18 months
Estimate Reduction in Opioid Use
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Background: PubMed 34745473Berardino 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.
- Background: PubMed 28403427Brummett 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.
- Background: PubMed 29733094Dunn 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.
- Background: PubMed 19675510Martin 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.
- Background: PubMed 39087325Luby 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.
- Background: PubMed 21173206Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
- Background: PubMed 21369752Banks ML, Roma PG, Folk JE, Rice KC, Negus SS. Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis. Psychopharmacology (Berl). 2011 Aug;216(3):431-9. doi: 10.1007/s00213-011-2235-2. Epub 2011 Mar 3.
- Background: PubMed 9141069Davidson EM, Coggeshall RE, Carlton SM. Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport. 1997 Mar 3;8(4):941-6. doi: 10.1097/00001756-199703030-00025.
- Background: PubMed 9113174Stubhaug A, Breivik H. Long-term treatment of chronic neuropathic pain with the NMDA (N-methyl-D-aspartate) receptor antagonist ketamine. Acta Anaesthesiol Scand. 1997 Mar;41(3):329-31. doi: 10.1111/j.1399-6576.1997.tb04693.x. No abstract available.
- Background: PubMed 19717013Sotgiu ML, Valente M, Storchi R, Caramenti G, Biella GE. Cooperative N-methyl-D-aspartate (NMDA) receptor antagonism and mu-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain. Pharmacol Res. 2009 Oct;60(4):284-90. doi: 10.1016/j.phrs.2009.04.002. Epub 2009 Apr 11.
- Background: PubMed 10215686Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999 May;289(2):1048-53.
- Background: PubMed 8657426Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain. 1995 Sep;62(3):259-274. doi: 10.1016/0304-3959(95)00073-2.
- Individual participant dataSharing planned: Yes. The investigator plans to share information by presenting abstract/journal materials pending results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Shobana Rajan, MD principal investigator
The Cleveland Clinic
Andra Duncan, MD study chair
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone in people with Post Operative Pain and Spinal Surgery, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stephanie Stoianoff, MBA (12164440231, stoians@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility and Acceptability-Participant Willingness/Recruitment (time frame: 7 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07222072, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.