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

Trial Summary

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 data supports the effectiveness of the drug combination of Methadone and Ketamine for pain management in liver transplant patients?

Research shows that combining ketamine with other pain medications like morphine can extend the duration of pain relief after surgery. Additionally, using methadone with ketamine has been found to reduce the need for other pain medications after surgery, suggesting that this combination could be effective for managing pain in liver transplant patients. ^{1 2 3 4 5}

Is the combination of methadone and ketamine generally safe for pain management?

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 cognitive issues. In cirrhotic patients, a small dose of ketamine with morphine was effective for pain relief without significant side effects. ^{2 3 4 6 7}

How is the drug combination of methadone and ketamine unique for pain management in liver transplant patients?

The combination of methadone and ketamine is unique because it potentially reduces the need for opioids after surgery by working together to manage pain more effectively, which is particularly beneficial for liver transplant patients who may have a history of substance use disorder. ^{2 4 8 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to learn if using methadone and ketamine during an adult deceased donor liver transplant can help decrease pain after surgery. The main questions it aims to answer are: * What impact does using methadone and ketamine during a deceased donor liver transplant have on pain after surgery? * Does the use of methadone and ketamine also have an impact on mental confusion (delirium) after surgery? Researchers will compare the use of methadone and ketamine to standard of care to see if the two drugs work to decrease pain and impact delirium after liver transplant. Participants will: * Receive either methadone and ketamine or standard of care during their deceased donor liver transplant. * Allow researchers to follow medical care throughout inpatient stay.

Research Team

Ryan Nazemian, MD, PhD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery. [2019]

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

Postoperative pain relief after hepatic resection in cirrhotic patients: the efficacy of a single small dose of ketamine plus morphine epidurally. [2019]

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

Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blinded, randomized controlled trial. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The perioperative combination of methadone and ketamine reduces post-operative opioid usage compared with methadone alone. [2018]

5. Iran pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial. [2022]

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

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis. [2023]

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

Comparison of the Effect of Intravenous Fentanyl with Low-Dose Ketamine on Pain Relief in Patients Taking Methadone and Suffering from Limb Fractures. [2023]

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

Opioid Avoidance in Liver Transplant Recipients: Reduction in Postoperative Opioid Use Through a Multidisciplinary Multimodal Approach. [2021]

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

A Successful Case of Switching Treatment from Ketamine to Methadone for Complex Neuropathic Pain. [2022]

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

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial. [2022]