Reducing Pain With Methadone and Ketamine in Liver Transplant

NCT ID: NCT06868589

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2026-09-01

Brief Summary

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.

Detailed Description

Pain control following liver transplantation (LT) has been the subject of interest of many research projects due to invasive nature of the procedure, significant comorbidities of recipients, effect of hepatic metabolism on many common pain medications and difficulties in performing some neuraxial and regional techniques given patient coagulopathy. Some newer regional nerve blocks such as External Oblique Intercostal (EOI) block has also been successfully utilized in pain management of patients undergoing liver resections but their utilization in perioperative setting for high-MELD patients and after-hour operations are limited. Methadone and ketamine are well-known drugs that have been recently emerged as components of new pain management pathways in many open surgeries due to their availability, cost, well-known metabolism, good safety profile and prolonged effects. Evidence has emerged that their use is associated with decreased likelihood of development of chronic pain and need for long term opioids. The combination of methadone and ketamine has been shown to be superior to opioids alone due to synergistic effect on N-methyl-d-aspartate and μ-opioid receptors. But these medications have not been extensively studied in LT recipients except for a few case reports and small studies. Current standards of care for intraoperative pain management during LT are systemic short and medium long-acting opioids such as fentanyl and hydromorphone which both have numerous concerns such as respiratory depression and opioid dependency. The aim of this study is to prospectively evaluate the effect of intraoperative methadone and ketamine administration on postoperative pain in liver transplant recipients. These drugs have been safely used during liver transplantation at LHMC and other centers and showed to be effective and safe, but the exact dosing and timing of administration requires further studies.

Conditions

Liver Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

M+K group

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

Group Type: EXPERIMENTAL

Methadone

Intervention Type: DRUG

Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation

ketamine

Intervention Type: DRUG

Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation

SOC group

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

Group Type: ACTIVE_COMPARATOR

Hydromorphone

Intervention Type: DRUG

Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure

fentanyl

Intervention Type: DRUG

Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure

Interventions

Methadone

Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation

Intervention Type: DRUG

ketamine

Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation

Intervention Type: DRUG

Hydromorphone

Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure

Intervention Type: DRUG

fentanyl

Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients ≥ 18 years of age at the time of LT.
• Undergoing LT 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

• Living donor liver transplantation (LDLT).
• Split liver transplantation (isolated right or left lobe).
• Acute liver failure (ALF) as the indication for LT.
• Repeat (redo) liver transplant
• Simultaneous liver and kidney transplant (SLK)
• Sedation or high vasopressor use.
• Subject is intubated and/or mechanically ventilated prior to entering the operating room for LT.
• Severe Hepatic encephalopathy
• History of psychiatric disorders such as schizophrenia or bipolar mood disorders
• History of chronic opioid use, substance abuse or opioid maintenance therapies
• Any history of allergic reaction to any of the study drugs History of Brugadda, prolonged QT syndrome or QTc in preoperative setting
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
• Prisoner
• Pregnant person
• Operational Exclusion Criterion: Subjects will not be enrolled if study personnel required for protocol execution (e.g., study investigator, research staff or pharmacy staff) are unavailable at the time of transplantation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lahey Clinic

OTHER

Sponsor Role: lead

Responsible Party

Ryan Nazemian

Staff Anesthesiologist: Division of Transplant, Director: Transplant Anesthesia Fellowship, Co-Director: Anesthesia Informatics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ryan Nazemian, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ryan Nazemian, MD, PhD

Role: CONTACT

ryan.nazemian@lahey.org

781-813-0389

Michael D Kaufman, MD

Role: CONTACT

michael.kaufman@bilh.org

9787026578

Facility Contacts

LHMC Department of Anesthesiology

Role: primary

ryan.nazemian@lahey.org

781-744-8132

Other Identifiers

20243140

Identifier Type: -

Identifier Source: org_study_id