Methadone-Based Analgesia for Scoliosis Surgery

(PRECISE Trial)

Overseen By Carly Riedmann, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Senthil Sadhasivam

Must not be taking: Opioids

Disqualifiers: Adults, Pregnancy, Severe sleep apnea, 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: 1

Duration: Up to 1 week post-operative

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pain management approach for children undergoing surgery for scoliosis, a spine condition. Researchers aim to determine if methadone, a strong pain reliever, can manage pain more effectively and aid faster recovery with fewer additional painkillers. The trial includes two groups: one receives methadone, and the other follows standard pain management without it. Eligible participants have idiopathic scoliosis, are scheduled for spine surgery, and either they or their guardians can speak and read English or Spanish. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it excludes those who are already using opioids before surgery.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, patients who received methadone during spine surgery needed fewer additional pain medications afterward. They reported less pain and greater satisfaction with their pain management. Another study found that methadone reduced pain and nausea after surgery. Research has shown that methadone is a safe option for managing pain in spinal surgeries. However, like all treatments, it can have side effects, so patients must be monitored closely. Since this trial is in an advanced phase, methadone's safety is likely well-understood, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about methadone-based analgesia for scoliosis surgery because it offers a potentially more effective pain management option compared to traditional opioid protocols. Unlike standard treatments that typically involve a variety of opioids, methadone provides consistent pain relief with fewer doses due to its long-acting properties. This approach could reduce the need for multiple medications and minimize opioid-related side effects and complications. By incorporating methadone into the Enhanced Recovery After Surgery (ERAS) protocol, this method aims to improve recovery times and patient comfort in the postoperative setting.

What evidence suggests that this methadone-based ERAS protocol is effective for scoliosis surgery?

Research has shown that methadone effectively relieves pain after spine surgery. In this trial, participants in the Methadone-Based ERAS Group will receive methadone as part of their pain management protocol. One study found that administering methadone during surgery reduced the need for other strong painkillers and improved pain management. Another study demonstrated that patients experienced less pain and required fewer pain medications after surgery when methadone was used. Methadone's longer duration of action helps control pain more effectively after surgery compared to short-term painkillers. Overall, methadone reduces pain and the need for additional painkillers, making recovery smoother and more comfortable. ^{1 2 3 5 6}

Who Is on the Research Team?

Senthilkumar Sadhasivam, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for children undergoing elective spine fusion surgery to correct scoliosis, including idiopathic scoliosis. Specific eligibility criteria are not provided, but typically include a certain age range and health status.

Inclusion Criteria

ASA physical status 1&2

I am between 10 and 17 years old.

I am having surgery for scoliosis not caused by other conditions.

Exclusion Criteria

Baseline prolonged QTc

Developmental delay

I have a neurological condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either methadone-based ERAS or standard-of-care non-methadone-based analgesia during and after spinal fusion surgery

Up to 1 week post-operative

Inpatient hospital stay

Follow-up

Participants are monitored for safety and effectiveness, including pain scores, opioid use, and adverse events

3 months

Week 1 post-discharge, Month 1, and Month 3

Long-term monitoring

Participants are assessed for chronic persistent surgical pain and opioid dependence

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview

The study compares two post-surgery recovery protocols: one using methadone (a strong painkiller) and another with standard care that doesn't use methadone. Children will be randomly placed in either group by chance.

How Is the Trial Designed?

Group I: Methadone-Based ERAS Group Experimental Treatment 1 Intervention

The methadone-based standardized analgesia intervention arm will include standardized perioperative care and analgesia, including intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.1 mg/kg up to a maximum of 5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral or IV doses of methadone (0.1 mg/kg up to a maximum of 5 mg) every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.

Group II: Non-Methadone-Based Group Active Control 1 Intervention

The comparator standard-of-care non-methadone-based analgesia arm will include standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards.

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?

Senthil Sadhasivam

Lead Sponsor

Trials

7

Recruited

4,200+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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The aim of this current concept review is to document the efficacy, safety, and the quality of evidence for different methods of pain management after PSF for ...