Rectal Methadone for Postoperative Pain

(PROMISE Trial)

Overseen By Janneth A Pazmino-Canizares, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sergio

Must not be taking: MAO inhibitors

Disqualifiers: Pregnancy, Respiratory issues, Opioid use, others

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

Compensation: Varies

Number of Visits: 2

Duration: During surgery

40 Participants Needed

Trial Summary

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 have used MAO inhibitors in the last 14 days or if you are taking more than 90 mg of morphine equivalents daily.

What data supports the effectiveness of the drug Rectal Methadone for postoperative pain?

Research shows that methadone, when used before or during surgery, can help reduce the need for other pain medications like morphine after surgery. It has been found to provide effective pain relief and may help manage pain better in patients who have undergone surgery. ^{1 2 3 4 5}

Is rectal methadone safe for use in humans?

Methadone, used for pain relief after surgery, has some safety concerns like risk of breathing problems and heart rhythm issues. It can also cause side effects such as nausea, vomiting, and sedation, especially at high doses. More research is needed to fully understand its safety in different forms and settings. ^{4 6 7 8 9}

How is rectal methadone different from other drugs for postoperative pain?

Rectal methadone is unique because it offers an alternative administration route compared to the more common oral or intravenous methods, potentially providing better bioavailability and convenience for patients who cannot take medications orally. Additionally, methadone's long-lasting effects and multiple mechanisms of action, including reducing tolerance to other opioids, make it a distinctive option for managing postoperative pain. ^{2 4 6 9 10}

What is the purpose of this trial?

Patients undergoing spinal surgery require pain control medication after their surgery. Investigators have successfully used intravenous Methadone to manage pain after surgery. However, doctors in Canada do not have the intravenous form of Methadone to prescribe to their patients. The investigators in Canada propose a pilot trial to investigate whether Methadone administered rectally could be used to manage pain after spinal surgery. The main questions are: 1. Are investigators able to recruit participants for this trial and learn from this study to plan a larger trial? 2. Does Methadone administered rectally during surgery, reduce participants' pain intensity, use less pain medication, and have a better recovery after surgery? Investigators will compare Methadone to a placebo (a look-alike substance that contains no drug) to see if Methadone works to manage pain after surgery better than the usual pain management. Participants will: * receive either Methadone or placebo during surgery. * be asked some questions about their pain during days 1 to 3 after surgery * be contacted by phone to ask about their recovery At this time, the study aims to recruit 40 participants from St. Michael's Hospital, to learn whether it will be feasible to plan a larger study.

Research Team

Sergio Pereira, MD PhD

Principal Investigator

St. Michael's Hospital. Unity Health Toronto

Eligibility Criteria

This trial is for adults aged 18-65 scheduled for elective spinal surgery with fusion at any level from sacral to cervical. They must be able to consent and, if of childbearing potential, agree to use contraception.

Inclusion Criteria

I am using birth control.

I can understand and agree to the study's requirements.

I am scheduled for elective spinal surgery with fusion.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Methadone or placebo rectally during spinal surgery

During surgery

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for pain intensity and recovery during the first three days after surgery

3 days

Daily assessments (in-person)

Follow-up

Participants are contacted by phone to assess recovery and pain interference 30 days after surgery

30 days

1 visit (virtual)

Treatment Details

Interventions

• Rectal Methadone

Trial Overview The study tests rectal Methadone's effectiveness in managing postoperative pain after spinal surgery compared to a placebo. It aims to determine if this method can reduce pain intensity, lower the need for other pain medications, and improve recovery.

Participant Groups

Group I: Intervention Arm with Methadone Experimental Treatment 1 Intervention

During the spinal surgery intervention, participants receive a single dose of 0.2mg/kg of Methadone rectally, after anesthesia induction.

Group II: Placebo arm Placebo Group 1 Intervention

During the spinal surgery intervention, participants receive a single dose of saline solution rectally after anesthesia induction.

Who Is Running the Clinical Trial?

Sergio

Lead Sponsor

Trials

1

Recruited

40+

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

AFP Innovation Fund

Collaborator

Trials

9

Recruited

1,500+

Findings from Research

In a study of 298 surgical patients, over 90% were already on methadone before surgery, highlighting the prevalence of chronic opioid use in this population.

Newly initiated post-operative methadone was linked to a higher risk of respiratory depression, particularly in older male patients, indicating the need for careful monitoring and management of analgesia in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative methadone prescribing and association with respiratory depression. Bova, SE., Kruer, RM., Nesbit, SA., 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]

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 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 60 women undergoing cesarean sections, subcutaneous methadone significantly reduced pain severity and increased patient satisfaction compared to standard pain management, indicating its effectiveness as a pain reliever.

The use of subcutaneous methadone was found to be safe for post-operative pain control, suggesting it could be a beneficial option for improving maternal and neonatal health during the early postpartum period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the analgesic effect of subcutaneous methadone after cesarean section. Jabalameli, M., Kalantari, F.[2021]

Methadone may be an effective option for postoperative pain control in children and adolescents, potentially reducing pain, opioid consumption, and the length of hospital stays, while also minimizing some side effects associated with traditional opioids.

Despite its benefits, methadone carries risks such as nausea, sedation, and QTc prolongation, highlighting the need for careful dosing protocols and further research to establish its safety and efficacy in various surgical contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What we know and what we don't know about the perioperative use of methadone in children and adolescents. Boisvert-Plante, V., Poulin-Harnois, C., Ingelmo, P., et al.[2023]

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]

References

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

Perioperative methadone prescribing and association with respiratory depression. [2021]

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

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

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. England pubmed.ncbi.nlm.nih.gov

Use of Methadone to Reverse Opioid Escalation in a Patient With Surgical Pain. [2019]

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

Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. [2022]

6. Denmark pubmed.ncbi.nlm.nih.gov

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

7. India pubmed.ncbi.nlm.nih.gov

Evaluation of the analgesic effect of subcutaneous methadone after cesarean section. [2021]

8. France pubmed.ncbi.nlm.nih.gov

What we know and what we don't know about the perioperative use of methadone in children and adolescents. [2023]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Bioavailabilities of rectal and oral methadone in healthy subjects. [2018]