Methadone + Ketamine for Pain Management in Liver Transplant

(RELIEF-LT Trial)

Overseen By Michael D Kaufman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Lahey Clinic

Must not be taking: Opioid therapies

Disqualifiers: Acute liver failure, Schizophrenia, Bipolar, 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: Intraoperative

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if methadone and ketamine during a liver transplant can reduce pain and mental confusion (delirium) afterward. Researchers will compare these drugs to the usual pain medications to identify which works better. It suits adults undergoing a liver transplant from a deceased donor who do not have severe mental health issues or a history of drug allergies. Participants will receive either methadone and ketamine or standard pain treatments during surgery. As a Phase 4 trial, this research helps clarify how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have a history of substance abuse or are on opioid maintenance therapies, you may not be eligible to participate.

What is the safety track record for methadone and ketamine?

Research has shown that using methadone and ketamine together can reduce the need for other pain medications after surgery, effectively managing pain. However, some individuals might experience side effects like vivid dreams. This combination has been studied specifically in liver transplant patients, but if the liver isn't functioning well, ketamine might cause brain swelling.

Methadone and ketamine are generally considered safe when used carefully. Methadone, FDA-approved for other uses, has been well-understood due to its long history. Ketamine is also a good alternative to traditional painkillers like morphine, especially in emergencies.

This trial is in a later phase, indicating that there is already substantial information about safety. However, as with any treatment, weighing the benefits against potential side effects is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using methadone and ketamine for pain management in liver transplant patients because these treatments offer a novel approach compared to the standard pain medications like hydromorphone and fentanyl. Methadone has a unique mechanism of action, working on different pain pathways and providing long-lasting relief, while ketamine targets NMDA receptors, potentially reducing pain and opioid use. This combination could offer more effective and sustained pain control with possibly fewer side effects than the current standard therapies.

What evidence suggests that methadone and ketamine might be effective for pain management in liver transplant?

This trial will compare the effectiveness of methadone combined with ketamine to the standard of care for pain management in liver transplant patients. Studies have shown that using methadone and ketamine together can reduce pain after surgery. Research suggests this combination may decrease the need for other pain medications, leading to fewer side effects. Methadone provides long-lasting pain relief, while ketamine blocks pain signals in the brain. Together, they might better manage pain, especially in complex surgeries like liver transplants. However, some individuals may experience side effects such as vivid dreams. Overall, this combination has effectively reduced post-surgery pain for liver transplant patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Ryan Nazemian, MD, PhD

Principal Investigator

Lahey Hospital and Medical Center, Department of Anesthesiology, Perioperative and Pain Medicine

Are You a Good Fit for This Trial?

This trial is for adults undergoing a deceased donor liver transplant, aiming to reduce post-surgery pain. Participants will be observed throughout their hospital stay.

Inclusion Criteria

I am receiving a liver transplant from a deceased donor.

Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

Exclusion Criteria

I am receiving a liver transplant from a living donor.

Any history of allergic reaction to methadone or ketamine

I am on a breathing machine before my liver transplant surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either methadone and ketamine or standard of care during their deceased donor liver transplant

Intraoperative

1 visit (in-person)

Postoperative Monitoring

Participants are monitored for pain management, delirium, and respiratory complications post-surgery

Up to 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Methadone

Trial Overview The study tests if methadone and ketamine during surgery can lessen pain and affect mental clarity after the procedure, compared to standard pain management practices.

How Is the Trial Designed?

Group I: M+K group Experimental Treatment 2 Interventions

Participants in this arm will receive the intervention with methadone and ketamine

Group II: SOC group Active Control 2 Interventions

Participants in this arm will receive the standard of care with combination of hydromorphone and fentanyl

Who Is Running the Clinical Trial?

Lahey Clinic

Lead Sponsor

Trials

74

Recruited

245,000+

Published Research Related to This Trial

A systematic review of 36 randomized controlled trials involving 3572 patients found that perioperative intravenous ketamine does not significantly reduce the incidence of chronic postsurgical pain after 6 months compared to placebo.

However, ketamine may lower the incidence of chronic postsurgical neuropathic pain after 3 months, although it also increases the risk of postoperative side effects like nystagmus and visual disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis. Abouarab, AH., Brülle, R., Aboukilila, MY., et al.[2023]

Citations

1. withpower.com withpower.com/trial/methadone-ketamine-for-pain-management-in-liver-transplant-81ff2

Methadone + Ketamine for Pain Management in Liver ... Research shows that combining methadone and ketamine can reduce the need for other opioids after surgery, but there may be side effects like vivid dreaming and ...

2. alicantobidmc.org alicantobidmc.org/resources/reducing-pain-methadone-and-ketamine-liver-transplant

Reducing Pain With Methadone and Ketamine in Liver ... The aim of this study is to prospectively evaluate the effect of intraoperative methadone and ketamine administration on postoperative pain in liver transplant ...

3. lidsen.com lidsen.com/journals/transplantation/transplantation-07-04-198

Multimodal Pain Management of Liver Transplantation Optimal management of perioperative analgesia regarding immediate and short‐term outcomes after liver transplantation–A systematic review ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4577640/

Analgesia after liver transplantation - PMC This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT).

5. brieflands.com brieflands.com/journals/hepatmon/articles/55414

Opioid Drugs in Patients With Liver Disease: A Systematic ... Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids.

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814327

Ketamine Compared With Morphine for Out-of-Hospital ... These findings show that ketamine was not inferior to morphine for pain control and is an opioid-reduction alternative for treatment of out-of-hospital acute ...