Methadone vs Morphine for Postoperative Pain

Overseen By Priyanka Singla, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must not be taking: Methadone, Buprenorphine, Naltrexone

Disqualifiers: Chronic pain, Pregnancy, Substance use disorder, others

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

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

Compensation: Varies

Number of Visits: 24

Duration: 72 hours

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of intravenous (IV) methadone in easing pain after major abdominal surgery compared to intrathecal (IT) morphine, which is injected near the spinal cord. The researchers aim to determine if methadone can provide similar pain relief while being less invasive and potentially reducing the need for additional painkillers. They seek participants undergoing midline abdominal surgery who can understand English and manage daily activities without regular opioid pain medication. The findings could enhance recovery experiences by offering a simpler pain management option. As an Early Phase 1 trial, this research focuses on understanding methadone's effects in people, allowing participants to contribute to pioneering pain management advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using daily opioids or medications for opioid use disorder, you may not be eligible to participate.

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

Studies have shown that administering methadone through an IV can reduce post-surgery pain. Most studies found it as safe as other pain medications, with similar side effects. Thus, methadone can alleviate pain without causing more issues than other painkillers.

Methadone also appears to reduce the need for additional pain medications after surgery, potentially leading to fewer side effects like nausea. However, this treatment remains in the early testing stages for this specific use. While some evidence suggests its effectiveness, more research is needed to fully understand its safety in this context. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Methadone is unique because it is administered intravenously, allowing for precise dosage control and rapid onset of pain relief. Unlike standard postoperative pain treatments like oral opioids or intrathecal morphine, methadone provides a longer-lasting effect due to its extended half-life. Researchers are excited about methadone because it targets both immediate pain relief and sustained pain management, potentially reducing the need for frequent dosing and minimizing the risk of breakthrough pain.

What evidence suggests that this trial's treatments could be effective for postoperative pain?

Research has shown that administering methadone through an IV can effectively manage post-surgical pain. In this trial, some participants will receive intravenous methadone, which studies have found provides long-lasting pain relief and reduces the need for additional painkillers. Methadone has been noted to lower pain levels and decrease nausea and vomiting after surgery. Patients receiving methadone often use fewer painkillers afterward compared to those receiving other treatments. Methadone effectively controls pain by acting on specific parts of the brain. Meanwhile, other participants in this trial will receive intrathecal morphine, serving as an active comparator. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients undergoing major abdominal surgery who need pain management post-surgery. It's not suitable for those with blood clotting issues or low platelet counts, as they can't receive intrathecal morphine.

Inclusion Criteria

Ability to understand and read English

Body mass index (BMI) between 18.5 and 45

I am an adult with a health status rated between 1 to 3 by the ASA.

Exclusion Criteria

I am unable or unwilling to sign the consent form.

I have had a spinal fusion surgery.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Intrathecal Morphine or Intravenous Methadone prior to incision for pain management during major abdominal surgery

72 hours

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of pain and quality of recovery

92 days

Multiple assessments at 24, 48, 72 hours, 42 days, and 92 days

What Are the Treatments Tested in This Trial?

Interventions

• Methadone
• Morphine

Trial Overview The study compares two pain control methods after abdominal surgery: IV methadone and IT morphine. The goal is to see if methadone, a noninvasive option, controls pain just as well without the side effects of morphine.

How Is the Trial Designed?

Group I: Intravenous Methadone Experimental Treatment 1 Intervention

0.2 mg / kg Intravenous delivery prior to incision. Maximum dosage will be 20 mg.

Group II: Intrathecal Morphine Active Control 1 Intervention

250 mcg Intrathecal Injection prior to incision

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?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

In a study involving 64 patients undergoing gynecological surgery, methadone provided superior pain relief compared to morphine on the second postoperative day.

Patients receiving methadone consumed significantly less opioid overall and experienced no serious side effects, such as respiratory depression, indicating it is a safer alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone versus morphine for postoperative pain in patients undergoing surgery for gynecological cancer: A randomized controlled clinical trial. Mercadante, S., David, F., Villari, P., et al.[2021]

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 study of 52 cancer patients, rotating to methadone for pain management was effective, achieving adequate pain relief in 89% of patients within 3 days, particularly for those with mixed nociceptive-neuropathic pain.

The study suggests that using a fixed equianalgesic ratio of 10:1 for patients with a morphine-equivalent daily dose (MEDD) under 400 mg may be sufficient, indicating a tailored approach to opioid rotation can enhance pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone rotation for cancer pain: an observational study. Tan, C., Wong, JF., Yee, CM., et al.[2022]

In a study of 30 women undergoing abdominal hysterectomy, those who received methadone for postoperative pain management reported significantly lower pain scores and required fewer additional opioids compared to those who received morphine.

Patients in the methadone group experienced a less painful overall postoperative course, with no significant respiratory depression or excessive sedation observed in either treatment group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Chui, PT., Gin, T.[2022]

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]

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]

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. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07092475

The Impact of Intraoperative Methadone on Postoperative ... Unlike short-acting opioids, a single dose of methadone given intraoperatively has been shown to be capable of maintaining analgesic levels for ...

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

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.

4. bjaopen.org bjaopen.org/article/S2772-6096(23)00098-9/fulltext

Clinical effectiveness and safety of intraoperative ... The postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0–61] mg vs 48 [31 ...

5. jpain.org jpain.org/article/S1526-5900(20)30044-4/fulltext

Methadone in Pain Management: A Systematic Review The primary outcome was analgesic effectiveness, and the secondary outcomes were side effects and cost. A search of PubMed, Medline, Embase, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31613867/

a systematic review and meta-analysis Patients in the methadone group generally reported lower postoperative pain scores in 7 of 10 studies. Meta-analysis revealed greater satisfaction scores with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37285308/

The Effects of Intraoperative Methadone on Postoperative ... The majority of studies indicated that methadone was superior to other opioids in reported pain scores, while the frequency of adverse events was similar ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772609623000989

Clinical effectiveness and safety of intraoperative ... Methadone only reduced postoperative pain at PACU arrival compared with morphine, and the observed side-effects and the proportion of same-day discharge were ...