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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to learn if oral methadone given before surgery works to minimize post-operative pain and opioid usage. The main questions it aims to answer are: Does oral methadone improve post-operative pain scores as compared to standard treatment? Does oral methadone lead to reduced use of post-operative and post-discharge opioid usage as compared to the current standard treatment? Researchers will compare oral methadone to a placebo (a look-alike substance that contains no drug) to assess the questions above. Participants will: Receive either oral methadone or a look-alike placebo before surgery Receive standard intraoperative and immediate post-operative pain control at the anesthesiologist's discretion Be asked about their pain levels in the recovery area Keep a diary of pain and opioid usage over the first 2 days after surgery

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 oral methadone safe for post-surgery pain management?

Methadone has been shown to reduce the need for other pain medications after surgery and generally provides good pain relief, but it carries risks such as respiratory depression (trouble breathing) and arrhythmia (irregular heartbeat). It is important to weigh these risks against its benefits, and more studies are needed to fully understand its safety compared to other pain treatments. ^{1 2 3 4 5}

How is the drug methadone unique for post-surgery pain relief?

Methadone is unique for post-surgery pain relief because it has a long-lasting effect, reducing the need for additional pain medication. It works by blocking certain receptors in the brain and also affects serotonin and noradrenaline, which can help manage pain more effectively than some other opioids. ^{2 6 7 8 9}

What data supports the effectiveness of the drug methadone for post-surgery pain?

Research shows that methadone can reduce the need for other pain medications after surgery and generally leads to lower pain scores and higher satisfaction with pain relief. However, it is important to consider potential risks like breathing problems and heart rhythm issues. ^{1 2 6 9 10}

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

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]

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]

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]

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 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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Postoperative pain control with methadone following lower abdominal surgery. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Intraoperative methadone administration and postoperative pain control: a systematic review and meta-analysis. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

A preoperative single dose of methadone for moderate-to-severely painful surgery reduces postoperative morphine consumption. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. [2023]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Opioid versus opioid-free analgesia after surgical discharge: protocol for a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Patient-controlled analgesia with oral methadone in cancer pain: preliminary report. [2020]

10. Denmark pubmed.ncbi.nlm.nih.gov

[Intraoperative methadone for post-operative pain]. [2021]