Methadone for Postoperative Pain

Overseen By Lynnette Harris, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors, SSRIs

Disqualifiers: Severe liver/kidney dysfunction, Obesity, Illicit drug use, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: Surgery duration

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of methadone, an opioid medication, for managing pain after heart surgery. It tests three administration methods: a single dose, a split dose, and a balanced split dose. Individuals scheduled for heart surgery who have not used opioids regularly in the past month may be suitable candidates. The goal is to enhance patient recovery by alleviating post-surgery pain. As an Early Phase 1 trial, this research seeks to understand methadone's effects in people, providing participants an opportunity to contribute to innovative pain management strategies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as CYP3A4 inducers and inhibitors, and SSRIs (a type of antidepressant). If you are on these medications, you may need to stop them before participating.

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

Research has shown that a single dose of methadone during surgery is generally well-tolerated. Studies have found it can significantly reduce postoperative pain and decrease the need for additional opioids, without causing severe side effects. For example, one study found that patients who received a single dose experienced less pain and used fewer opioids in the first 24 to 48 hours after surgery.

Similarly, research indicates that administering methadone in split or balanced split doses also appears safe. Although less information is available, some studies suggest these methods can help manage pain after heart surgery without major side effects. Methadone is known for providing long-lasting pain relief, which can be beneficial during surgery.

Since this trial is in an early stage, it primarily aims to confirm these safety findings and determine the optimal dose for pain relief. Methadone is already approved by the FDA for treating pain and addiction, supporting its safety. However, its use specifically for heart surgery is still under investigation in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using methadone for postoperative pain because it offers a potentially longer-lasting pain relief compared to standard opioids like morphine and fentanyl. Methadone's unique mechanism allows it to act on multiple pain pathways, which could mean more effective pain management with fewer doses. Additionally, exploring different dosing approaches—like a single dose at anesthesia induction or split doses after surgery—might optimize its benefits and minimize side effects, offering a tailored approach to managing pain after surgery.

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

Research has shown that a single dose of methadone during surgery can reduce pain for up to 72 hours afterward. This approach allows patients to experience less pain and sometimes use fewer other pain medications. In this trial, some participants may receive a single dose of methadone at the induction of anesthesia. Others will receive methadone in split doses post-cardiopulmonary bypass, which studies have found can maintain consistent pain relief and reduce the need for additional opioids. Additionally, some participants will receive balanced split doses of methadone, potentially providing better pain control without requiring higher doses of other painkillers. Overall, methadone’s long-lasting effects make it a promising option for managing pain after heart surgery. ^{2 5 6 7 8}

Who Is on the Research Team?

Ettore Crimi, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals undergoing cardiac surgery who need pain management. The study aims to find the best methadone dosage for postoperative pain relief. Specific eligibility criteria are not provided, so participants should inquire with the trial coordinators.

Inclusion Criteria

Ability to provide informed consent

I am expected to be taken off a ventilator within 12 hours after surgery.

I am scheduled for heart surgery that involves opening my chest and using a heart-lung machine.

Exclusion Criteria

Left Ventricular Ejection Fraction <30%

Body mass index >40 kg/m²

Corrected QT interval interval >500 milliseconds

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive methadone during cardiac surgery with cardiopulmonary bypass using different dosing strategies

Surgery duration

1 visit (in-person)

Postoperative Monitoring

Plasma methadone concentration is measured at various intervals post-surgery to assess pharmacokinetics

72 hours

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain intensity and opioid consumption

3 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview

The study is testing different ways of giving methadone: a balanced split dose, a single dose, or a regular split dose during and/or after surgery. It seeks to determine which method is most effective in managing post-surgical pain.

How Is the Trial Designed?

Group I: Split dose of methadone Experimental Treatment 1 Intervention

Split dose of methadone post cardiopulmonary bypass

Group II: Balanced split dose of methadone Experimental Treatment 1 Intervention

Balanced split dose of methadone post cardiopulmonary bypass

Group III: Single dose of methadone Active Control 1 Intervention

Single dose of methadone administered at induction of anesthesia

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07226245

Methadone Pharmacokinetics in Cardiac Surgery

This study hopes to identify the optimal dose of methadone to use to treat this surgical pain. Detailed Description. The uncertainty regarding ...

2.

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 ...

3.

jopan.org

jopan.org/article/S1089-9472(21)00319-1/fulltext

Rediscovery of Methadone to Improve Outcomes in Pain ...

A single dose of 0.15 mg/kg of intraoperative methadone decreased total opioid consumption immediately after surgery and 30 days after discharge ...

4.

associationofanaesthetists-publications.onlinelibrary.wiley.com

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

Intravenous methadone for pain management in cardiac surgery

Methadone may improve pain control and decrease the need for postoperative opioids. Randomised controlled trials, however, are limited and the ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38528704/

The IMPOWR Network Divided or Single Exposure Study ...

Results: The study hypothesizes that persons assigned to the split dosing condition will report lower pain and opioid withdrawal relative to ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10978480/

The role of methadone in cardiac surgery for management ...

Intraoperative administration of methadone was associated with better pain control without significant side-effects after cardiac surgery.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1053077024009066

Intraoperative Methadone in Adult Cardiac Surgical ...

In a study comparing postoperative use of morphine versus methadone in cardiac surgery patients it was observed that methadone showed 22% higher analgesic ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05075265

Methadone in Adults Undergoing Cardiac Surgery

Patients with high levels of postoperative pain have 3.5 times the risk of chronic pain and their inadequate treatment can lead to chronic or neuropathic pain ...