Oral Methadone for Post-Surgery Pain

Overseen By Alexander Chen, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Keck School of Medicine of USC

Disqualifiers: Pregnant, Respiratory compromise, Opioid allergy, others

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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if taking oral methadone before surgery reduces pain and the need for other opioids afterward. Researchers compare methadone, an opioid pain medication, to a placebo, a pill with no active drug, to assess its effectiveness in pain management. Individuals undergoing elective knee or hip repair surgery and in good health may qualify for this study. Participants will take either methadone or a placebo before surgery and monitor their pain and opioid use for two days afterward. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking pain management solution.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that methadone is generally safe and effective for managing post-surgical pain. Studies have found that using methadone during surgery can enhance pain relief and reduce the need for additional pain medications afterward. For example, one study found that a single dose of methadone during surgery significantly reduced pain for the following two days. Another study showed that patients required less additional pain medication when methadone was used in heart surgeries. Importantly, these studies did not find an increase in negative side effects with methadone use.

Since this trial is in a late stage, methadone has already demonstrated safety in earlier research. Additionally, the FDA has approved methadone for other uses, further supporting its safety for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for post-surgery pain rely on short-acting opioids like morphine or oxycodone, which require frequent dosing and can lead to significant side effects. Methadone is unique because it is a long-acting opioid, which means it could provide more sustained pain relief with fewer doses. Researchers are excited about methadone because it has a different mechanism of action compared to traditional opioids, potentially offering more effective pain management with a lower risk of dependency. Additionally, methadone's longer duration of action could improve patient comfort and reduce the need for frequent medication, making recovery smoother.

What evidence suggests that oral methadone could be effective for post-surgery pain?

Research has shown that methadone, which participants in this trial may receive, can effectively reduce pain after surgery and lessen the need for other pain medications. Studies have found that patients receiving methadone report less pain and require fewer additional painkillers compared to those receiving treatments like fentanyl. Trials have also demonstrated that methadone provides better overall pain relief post-surgery. An important benefit of methadone is its potential to reduce opioid use, which might help lower the risk of dependency. Overall, methadone has shown promising results in managing post-surgical pain. ^{1 2 6 7 8}

Who Is on the Research Team?

Alexander Chen, M.D.

Principal Investigator

Keck School of Medicine of USC

Are You a Good Fit for This Trial?

This trial is for individuals scheduled for knee surgery or hip arthroscopy. Participants must meet certain health requirements, which are not specified here. People who do not meet these health standards or have conditions that could interfere with the study's outcomes will be excluded.

Inclusion Criteria

I am scheduled for elective knee or hip surgery and am medically fit for it.

Exclusion Criteria

Allergy to opioids

Pregnant or breastfeeding

I received a nerve block before surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-operative

Participants complete a survey on pain scores and opioid usage; receive either oral methadone or placebo before surgery

1 day

1 visit (in-person)

Intraoperative

Participants receive standard intraoperative pain control; intervention group receives oral methadone

Day of surgery

Post-operative

Participants are monitored in the PACU for pain scores and opioid usage; receive standard PACU medications

1 day

Follow-up

Participants are monitored for pain scores and opioid usage post-discharge; follow-up calls on post-operative day 1 and 2

2 days

2 calls (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Placebo

Trial Overview The trial is testing if taking oral methadone before surgery can reduce pain and the need for opioids after surgery compared to a placebo (a substance with no drug). Patients will either receive methadone or a placebo and track their pain and opioid use post-surgery.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 1 Intervention

5mg PO methadone for participants \<50kg or 10mg PO methadone for participants \>50kg

Group II: Control Placebo Group 1 Intervention

placebo sugar pill and standard intraoperative pain control using short-acting opioids, with drug choice and dosing at the practitioner's discretion

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?

Keck School of Medicine of USC

Lead Sponsor

Trials

7

Recruited

1,000+

Published Research Related to This Trial

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]

Intraoperative use of methadone significantly reduced postoperative pain scores at rest and during movement for up to 72 hours after surgery, based on a meta-analysis of 13 trials involving 486 patients.

Methadone also decreased total opioid consumption in the postoperative period, leading to better patient satisfaction compared to other opioids, indicating its efficacy as a pain management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. Machado, FC., Vieira, JE., de Orange, FA., et al.[2023]

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]

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 40 women undergoing lower abdominal surgery, those who received methadone reported significantly lower pain levels and required less additional pain relief compared to those who received morphine, indicating methadone's effectiveness for postoperative analgesia.

Methadone's long plasma half-life (approximately 54 hours) allows for sustained pain relief, making it a safe and effective alternative to morphine without notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative pain control with methadone following lower abdominal surgery. Richlin, DM., Reuben, SS.[2022]

In a meta-analysis of 10 studies involving 617 surgical patients, those who received methadone had significantly lower postoperative opioid consumption compared to those who received other opioids, with a mean difference of -15.22 mg in oral morphine equivalents.

Patients receiving methadone also reported lower pain scores and higher satisfaction with their pain management, although the use of methadone carries risks such as respiratory depression and arrhythmia that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis. D'Souza, RS., Gurrieri, C., Johnson, RL., et al.[2021]

A single dose of methadone (0.2 mg/kg) given at the start of anesthesia significantly reduced the need for morphine after surgery, with patients using less morphine in the Postanesthesia Care Unit (0 mg vs. 7 mg) and over the first 72 hours (19 mg vs. 35 mg).

Patient satisfaction regarding pain control was high in both the methadone and fentanyl groups, indicating that methadone is an effective option for managing postoperative pain without compromising patient comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preoperative single dose of methadone for moderate-to-severely painful surgery reduces postoperative morphine consumption. Bastian, K., Buehler, PK., Slizyte, D., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07222072

Methadone to Reduce Chronic Opioid Use After Major ... Methadone not only reduced the incidence of post-surgical pain in the study group. but also the percentage of patients who required opioid ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12152498/

Intraoperative methadone for postoperative pain in adult ... This study hypothesised that methadone would provide superior postoperative pain relief and reduced opioid consumption compared with fentanyl.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1089947225001066

Review Intraoperative Utilization of Intravenous Methadone ... In the included trials, methadone doses of 0.08 to 0.4 mg/kg of IBW demonstrated lower pain scores and reduced rescue opioid usage in the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6872483/

Intraoperative methadone for postoperative pain management Several recent trials have reported that intraoperative IV methadone is associated with significantly better postoperative analgesia. However, such studies are ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07092475

The Impact of Intraoperative Methadone on Postoperative ... Intra-operative Methadone Decreases Post-operative Pain and Opioid Use in DIEP Flap Breast Patients: A New ERAS Protocol. Plast Reconstr ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2772609625000425

Intraoperative methadone for postoperative pain in adult ... In conclusion, one dose of intraoperative methadone decreased pain intensity for the following 2 days after surgery and postoperative opioid consumption was ...

7. mdpi.com mdpi.com/2227-9032/13/19/2431

Perioperative Methadone in Orthopedic Surgery The methadone-based pathway significantly decreased 24 h pain scores (mean [95% confidence interval]: 4.8 [4–6] to 3.4 [2–4], p = 0.03), reduced total 24 h ...

8. associationofanaesthetists-publications.onlinelibrary.wiley.com associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16754

Intravenous methadone for pain management in cardiac surgery Giving methadone during heart surgery helped reduce pain afterwards and meant patients needed less extra pain medicine. It did not cause more ...