Methadone for Pain Management in Spinal Surgery

Overseen By Jess Brallier, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Methadone, Opioid antagonists

Disqualifiers: Drug misuse, Major psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether methadone, a type of pain medication, can manage pain more effectively than standard medications immediately after spinal surgery. Researchers aim to determine if administering methadone during surgery reduces the need for other painkillers in the first 72 hours post-surgery. Participants will receive either methadone or no methadone during their operation to compare outcomes. The trial seeks adults scheduled for spinal surgery involving metal supports, with an expected hospital stay of at least two nights post-procedure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in pain management.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using methadone or have used it in the past 6 weeks, or if you are using opioid antagonists like buprenorphine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using methadone or certain other drugs like opioid antagonists. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that methadone is likely to be safe for humans?

Research has shown that methadone, when used during surgery, is generally safe for patients. Studies have found it effectively reduces pain after major spine surgery without a high risk of serious side effects. Specifically, methadone use has been linked to fewer pain episodes and less intense pain in the weeks following surgery. Randomized trials demonstrated that methadone significantly reduces the need for additional pain medication after surgery.

Overall, patients who received methadone during surgery did not experience more side effects than those who did not receive it. This suggests methadone is a safe option for managing pain during and after spinal surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pain management?

Unlike standard pain management options for spinal surgery, which often rely on opioids like morphine or fentanyl, methadone is unique because it acts on multiple pain pathways in the brain. This dual-action mechanism not only targets the typical opioid receptors but also modulates NMDA receptors, which may help in managing pain more effectively and potentially reducing the development of opioid tolerance. Researchers are excited about methadone's potential to provide longer-lasting pain relief with a single dose during surgery, which could simplify pain management and enhance recovery for patients.

What evidence suggests that methadone might be an effective treatment for pain management in spinal surgery?

Research has shown that using methadone during surgery can manage pain more effectively after spinal surgery. In this trial, some participants will receive a methadone bolus during surgery. One study found that patients who received methadone needed less pain medication afterward and reported less pain, suggesting that methadone could enhance comfort and satisfaction with pain control post-surgery. Another study found that a single dose of methadone before surgery improved pain management for spine surgery patients. Overall, methadone appears promising in reducing the need for other pain medicines and improving recovery after surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Jess Brallier, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-75 scheduled for certain spinal surgeries lasting over 2 hours and a hospital stay of at least 2 nights can join. Excluded are those with recent methadone use, opioid antagonists, major psychiatric disorders, high BMI or heart issues, pregnant/breastfeeding women, kidney dysfunction, specific spine cases or drug misuse history.

Inclusion Criteria

I expect to stay in the hospital for at least 2 nights after surgery.

I am between 18-75 years old and scheduled for a specific spine surgery lasting 2+ hours.

Exclusion Criteria

I am currently taking medication that includes opioid blockers.

I cannot take certain pain medications like acetaminophen or opioids.

I have had spine surgery on less than 2 levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Treatment

Participants undergo spinal surgery with or without methadone administration to manage pain

During surgery

Post-operative Monitoring

Participants' pain levels and opioid requirements are monitored for 72 hours after surgery

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Saline placebo

Trial Overview The study is testing if methadone given during spinal surgery reduces pain and the need for other pain meds after surgery better than a saline placebo. Pain levels and additional medication needs will be compared between the two groups post-surgery.

How Is the Trial Designed?

Group I: Methadone bolus during surgery Active Control 1 Intervention

Patients will be administered methadone 0.2 mg/kg (max 20 mg).

Group II: No Methadone during surgery Active Control 1 Intervention

No Methadone during surgery

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Methadone is an effective option for managing severe cancer pain, especially neuropathic pain that doesn't respond well to other opioids or when side effects from those opioids are problematic.

There is a need for better understanding of methadone's pharmacokinetics and accurate dosage conversion, as many existing charts underestimate its potency, which can lead to a risk of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rediscovery of methadone for cancer pain management. Ayonrinde, OT., Bridge, DT.[2013]

Patients who received a single intraoperative dose of methadone during complex spine surgery reported significantly lower weekly frequency of chronic pain at 3 months post-surgery compared to those who received hydromorphone, indicating methadone's potential for long-term pain management.

In cardiac surgery patients, those who received methadone also experienced less frequent postsurgical pain at 1 month compared to those who received fentanyl, suggesting methadone's efficacy in reducing early postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery. Murphy, GS., Avram, MJ., Greenberg, SB., et al.[2023]

In a study of 1,478 patients undergoing major spine surgery, 36.8% experienced respiratory depression and 79.8% had hypoxemia after receiving intravenous methadone, indicating a significant risk of respiratory issues post-surgery.

Despite the high incidence of respiratory depression, the overall in-hospital mortality rate was low at 0.14%, suggesting that while methadone can lead to mild to moderate respiratory complications, it can be managed effectively with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients. Dunn, LK., Yerra, S., Fang, S., et al.[2020]

In a study of 120 patients undergoing spinal fusion surgery, those who received methadone experienced significantly lower opioid consumption post-surgery compared to those who received hydromorphone, with reductions observed on all three postoperative days.

Patients in the methadone group reported lower pain scores and higher satisfaction with pain management throughout the first three days after surgery, indicating that methadone may be a more effective option for postoperative pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Murphy, GS., Szokol, JW., Avram, MJ., et al.[2017]

Intraoperative administration of methadone has been shown to effectively reduce post-operative pain and decrease the need for additional opioids after surgery, leveraging its long elimination half-life.

This review highlights the potential benefits of using methadone in surgical settings and calls for further research to optimize its clinical application in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intraoperative methadone for post-operative pain]. Uhrbrand, CG., Friesgaard, KD., Brix, LD., et al.[2021]

The implementation of a methadone-based multimodal analgesia protocol in 122 idiopathic scoliosis patients significantly reduced the length of hospital stay from a median of 3 days to 2 days compared to the conventional pain management regimen.

Patients on the new protocol experienced lower total opioid consumption and improved pain control by postoperative day 2, along with a quicker return to bowel function, indicating enhanced recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone-based Multimodal Analgesia Provides the Best-in-class Acute Surgical Pain Control and Functional Outcomes With Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents With Idiopathic Scoliosis. Ye, J., Myung, K., Packiasabapathy, S., et al.[2022]

Methadone can be an effective option for patients with chronic pain who are undergoing opioid rotation, particularly for those with spinal cord injuries, due to its unique pharmacological properties.

However, methadone carries risks of serious adverse reactions and requires careful dosing and monitoring by experienced clinicians due to its complex pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid rotation: A case example using methadone in spinal cord injury. Pawasauskas, J.[2015]

Methadone is a unique opioid that not only acts on mu receptors but also has effects on delta receptors and NMDA receptors, making it a complex option for pain management, especially in cases of uncontrolled pain or when other opioids cause toxicity.

While methadone can be safer at lower doses, there are significant risks associated with high doses, including prolonged QT interval and potential for serious heart issues, highlighting the need for more research through randomized controlled trials to better understand its safety and efficacy compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. Bryson, J., Tamber, A., Seccareccia, D., et al.[2019]

A study involving adolescents aged 12-19 undergoing spinal surgery found that a single intravenous dose of 0.25 mg/kg methadone resulted in plasma concentrations that were below the minimum effective analgesic level within the first hour, indicating potential inadequate pain relief post-surgery.

To improve analgesic effectiveness, the researchers recommend following the initial bolus dose with a continuous infusion of 0.1-0.15 mg/kg/h for 4 hours, which could help maintain adequate plasma concentrations for effective pain management over 24 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of methadone in adolescents undergoing posterior spinal fusion. Stemland, CJ., Witte, J., Colquhoun, DA., et al.[2013]

A protocol using scheduled postoperative methadone significantly reduced opioid usage by 45% compared to a patient-controlled analgesia (PCA) strategy in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis, with 22 patients in the methadone group consuming only 0.18 mg/kg of hydromorphone equivalents.

Both pain and sedation scores were similar across all groups, indicating that the reduction in opioid use did not compromise pain management effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduled methadone reduces overall opioid requirements after pediatric posterior spinal fusion: A single center retrospective case series. Mok, V., Sweetman, S., Hernandez, B., et al.[2022]

In a study of 1010 patients undergoing spine surgery, oral methadone was found to be a feasible alternative to intravenous methadone, showing non-inferior pain scores and opioid consumption by postoperative day 3.

While the intravenous group required a higher preoperative and total opioid dose, there were no significant differences in adverse effects like QTc prolongation or arrhythmias between the two groups, suggesting that oral methadone is a safe option for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of oral versus intravenous methadone on postoperative pain and opioid use after adult spinal deformity surgery: A retrospective, non-inferiority analysis. Esfahani, K., Tennant, W., Tsang, S., et al.[2023]

A study of 39 patients undergoing opioid rotation from methadone to alternative opioids found that the mean dose ratio for oral methadone to oral morphine equivalent daily dose was 1:4.7, and for intravenous methadone, it was 1:13.5, indicating significant differences in potency between the two forms.

The research suggests that these new dose ratios can help clinicians switch patients to alternative opioids more safely, especially when managing side effects or inadequate pain control from methadone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Walker, PW., Palla, S., Pei, BL., et al.[2018]

In a study of 29 patients undergoing complex spine surgery, a single dose of methadone significantly reduced postoperative opioid requirements by about 50% compared to a continuous sufentanil infusion at 48 and 72 hours after surgery.

Patients receiving methadone also reported lower pain scores, approximately 50% less pain at 48 hours post-surgery, while the incidence of side effects was similar between the methadone and sufentanil groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Gottschalk, A., Durieux, ME., Nemergut, EC.[2022]

Citations

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A Randomized, Double-blinded, Controlled Trial Intraoperative methadone administration reduced postoperative opioid requirements, decreased pain scores, and improved patient satisfaction with pain ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7392616/

Methadone-based Multimodal Analgesia Provides the Best-in ... Methocarbamol, in particular, has been proven to be safe and effective for acute lower back pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06843174

Perioperative Rectal Methadone in Spine Surgery The investigators in Canada propose a pilot trial to investigate whether Methadone administered rectally could be used to manage pain after spinal surgery.

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Methadone in Pain Management: A Systematic Review Overall, data on the effectiveness of methadone ... Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery.

5. jopan.org jopan.org/article/S1089-9472(21)00319-1/fulltext

Rediscovery of Methadone to Improve Outcomes in Pain ... Methadone may help improve pain management in patients undergoing spine surgery. For instance, a single dose of methadone (0.2 mg/kg) before ...

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Clinical Effectiveness and Safety of Intraoperative ... SEVERE pain in the early postoperative period remains a common yet underestimated and undertreated prob- lem. Despite advances in pain management strategies ...

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The Role of Methadone and Regional Anesthesia in ... The patients in the methadone group reported fewer episodes of pain per week three months after surgery and lower intensity of back pain ...

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Perioperative Methadone in Orthopedic Surgery Results: Randomized controlled trials in adult spine surgery consistently showed that intraoperative methadone (0.2 mg/kg) significantly reduced postoperative ...