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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rectally administered Methadone can control pain after spinal surgery. Researchers aim to determine if this method is more effective than a placebo, a look-alike substance with no active medicine. They are also assessing whether this approach reduces the use of other pain medications and improves overall recovery. Individuals undergoing elective spinal surgery with fusion who can provide informed consent may be suitable candidates for this study. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for rectal Methadone?

Research has shown that methadone is generally safe for managing post-surgical pain. Studies have found that methadone reduces pain and decreases the need for other painkillers. Compared to a placebo and other pain medications like morphine, methadone provides longer-lasting pain relief with fewer doses.

Recent studies support using methadone during surgery, indicating that serious side effects are uncommon. This finding reassures those considering participation in a trial involving methadone. It is well-tolerated for pain management.

This trial is in a later phase, indicating substantial information about methadone's safety from earlier research. While the rectal form is under study here, methadone is a well-known medication for pain and has been used safely in other forms. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard pain management options for postoperative pain, which often involve oral or intravenous opioids like morphine or fentanyl, rectal methadone offers a unique delivery method. This approach allows for a prolonged and steady release of the medication, potentially providing longer-lasting pain relief with a single dose. Researchers are excited about rectal methadone because it can be administered after anesthesia induction, potentially minimizing the need for additional opioids post-surgery and reducing the risk of opioid-related side effects. This could lead to more effective and safer pain management for patients undergoing spinal surgery.

What evidence suggests that rectal Methadone might be an effective treatment for postoperative pain?

Research has shown that Methadone effectively manages pain after surgery. In this trial, participants in the intervention arm will receive rectal Methadone. Studies have found that this method can provide longer-lasting pain relief and result in less pain compared to a placebo or other pain medications like morphine. Although some studies indicate that Methadone may not always reduce the need for additional painkillers, it generally increases patient satisfaction with pain management. Therefore, using rectal Methadone could be a promising option for pain relief after spinal surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

Sergio Pereira, MD PhD

Principal Investigator

St. Michael's Hospital. Unity Health Toronto

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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]

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 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]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06843174

Perioperative Rectal Methadone in Spine Surgery

The investigators in Canada propose a pilot trial to investigate whether Methadone administered rectally could be used to manage pain after spinal surgery.

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sciencedirect.com

sciencedirect.com/science/article/pii/S1526590020300444

Methadone in Pain Management: A Systematic Review

Methadone was associated with less pain, a longer duration of analgesia and lower postoperative analgesia requirements when compared to placebo, morphine, and ...

3.

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 ...

4.

joma.amegroups.org

joma.amegroups.org/article/view/5991/html

Retrospective cohort study on the effect of intraoperative ...

Conclusions: a single dose of intraoperative methadone improves postoperative pain after OMF surgeries but does not reduce postoperative opioid consumption.

5.

journals.lww.com

journals.lww.com/wjcs/fulltext/2023/12040/intraoperative_methadone_use_in_patients.3.aspx

Intraoperative Methadone Use in Patients Undergoing...

Our investigation found that the inclusion of intraoperative methadone does not reduce postoperative opioid use in laparoscopic colorectal surgery. Furthermore, ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12524262/

Perioperative Methadone in Orthopedic Surgery: A Scoping ...

Conclusions: Perioperative methadone is an effective analgesic adjunct that reduces postoperative pain and opioid requirements, especially in ...

7.

snacc.org

snacc.org/wp-content/uploads/2021/07/Perioperative-Methadone-and-Ketamine.pdf

Perioperative-Methadone-and-Ketamine.pdf

Recent literature has supported the safety of intraoper- ative methadone; studies have documented that the inci- dences of adverse outcomes did ...

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mdpi.com

mdpi.com/2035-8377/17/6/94

Comprehensive Approaches to Pain Management in ...

This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches.