Liver TransplantationPhase 4RELIEF-LTNCT06868589
Reducing Pain With Methadone and Ketamine in Liver Transplant
A Phase 4 study testing Methadone, ketamine and Hydromorphone in people with Liver Transplantation, run by Lahey Clinic at 2 sites in United States.
Trial 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?… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Methadone, ketamine and Hydromorphone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Jun 2025to 1 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Lahey Clinicc
Burlington, Massachusetts, 01805
Lahey Clinic
Burlington, Massachusetts, 01805
About this study
Official title: Randomized Clinical Trial of Methadone and Ketamine for Pain Management During Deceased Donor Liver Transplant
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:
Read more
- 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.
Read the 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
- Keywords
- Liver Transplantation, Deceased Donor Liver Transplant, Postoperative Pain, Methadone, Ketamine, Perioperative Analgesia, Anesthesiology, Acute Pain, Transplant Surgery, Opioids
- Medical subject headings
- Pain, Postoperative, Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation
ketamineDrug
Participants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation
HydromorphoneDrug
Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure
fentanylDrug
Participants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure
| Study group | Role | What they receive |
|---|---|---|
| M+K group | Experimental | Participants in this arm will receive the intervention with methadone and ketamine Receives: Drug: Methadone; Drug: ketamine |
| SOC group | Active comparator | Participants in this arm will receive the standard of care with combination of hydromorphone and fentanyl Receives: Drug: Hydromorphone; Drug: fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative Pain
postoperative opioid consumption (measured as morphine milligram equivalents ((MME)) 48 hours after surgery
Measured: 8, 16, 24, 32, 40 and 48hours post-surgery finish
Postoperative Pain
Subjective postoperative pain scores measured as 0-10 (10 being the worst pain)
Measured: 8, 16, 24, 32, 40 and 48hours post-surgery finish
Secondary outcomes (8)
Length of stay in intensive care unit
Duration of length of stay in intensive care unit in hours
Measured: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Length of stay in hospital
Duration of length of stay in the hospital in days
Measured: Post surgery finish until discharge from hospital, or date of death from any cause, whichever came first, assessed up to 30 days
Delirium
Incidence of postoperative delirium measured by standard CAM-ICU scores, ICD-10 diagnosis of delirium, any use of anti-agitation medication such as haloperidol, dexmedetomidine or seroquel
Measured: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Respiratory complications
Any significant respiratory complications such as re-intubation, need for invasive ventilation such as BIPAP or CPAP
Measured: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Narcotics reversal agent
Any need for narcotics reversal agents such as Naloxone after administration of study drugs
Measured: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Postoperative adjunct pain modalities
Incidence of usage of any additional pain modalities such as nerve blocks, neuraxial anesthesia, non-narcotic pain medications such as additional ketamine dose, ketorolac, methocarbamol, ketorolac, etc
Measured: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Correlation Between Study Drug Exposure and Early Post-Transplant Laboratory Markers of Liver Dysfunction
Unit of measure: Correlation coefficient (r) describing the association between study drug exposure and postoperative laboratory markers of liver dysfunction during the first 24hrs post surgery.
Independent variables (study drug exposure):
- Randomized study drug assignment (e.g., ketamine vs methadone vs standard of care)
- Total intraoperative dose of each study drug (total mg)
Dependent variables (markers of postoperative liver dysfunction):
Correlation coefficients will be calculated between study drug exposure and the following laboratory values measured during first postoperative days :
- Peak alanine aminotransferase (ALT), IU/L
- Peak aspartate aminotransferase (AST), IU/L
- Peak total bilirubin, mg/dL
- Peak international normalized ratio (INR)
Measured: Immediate to 24hrs post surgery finish
Correlation Between Donor and Surgical Factors and Postoperative Opioid Use (MME)
Unit of measure: Correlation coefficient (r) describing the association between each donor/surgical factor and total postoperative opioid consumption (MME) during postoperative days 0-2. Total MME will be calculated by converting all administered opioids into morphine milligram equivalents using standard conversion factors.
Factors assessed (independent variables):
- Donor age (years)
- Donation type (donation after brain death vs donation after circulatory death)
- Use of normothermic machine perfusion (yes/no)
- Cold ischemia time (hours)
- Warm ischemia time (minutes)
- Surgical technique characteristics (e.g., piggyback vs caval replacement approach, vascular anastomosis techniques, use of veno-venous bypass), coded as categorical variables
Measured: From the end of surgery through 48hr post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2025
- Study start30 Jun 2025
- Primary completion1 Mar 2026
- Study completion1 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned to either intervention or standard of care group at the ratio of 1:1
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lahey Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ryan Nazemian, Lahey Clinic
- Investigators
- Ryan Nazemian, MD, PhD, Principal investigator, Lahey Clinic, Department of Anesthesiology, Perioperative and Pain Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06868589
- Sponsor's protocol ID
- 20243140
- Acronym
- RELIEF-LT
- Status last verified
- Aug 2026
- First submitted
- 1 Mar 2025
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Sensitive transplant data will not be shared for patients privacy
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial of Methadone and Ketamine for Pain Management During Deceased Donor Liver Transplant
- ClinicalTrials.gov ID
- NCT06868589
- Acronym / sponsor ID
- RELIEF-LT / 20243140
- Conditions
- Liver Transplantation
- Keywords
- Liver Transplantation, Deceased Donor Liver Transplant, Postoperative Pain, Methadone, Ketamine, Perioperative Analgesia, Anesthesiology, Acute Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Lahey ClinicUniversity, hospital or other
- Study start
- 30 Jun 2025 (actual)
- Primary completion
- 1 Mar 2026 (actual)
- Study completion
- 1 Jun 2026 (actual)
- First posted
- 11 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned to either intervention or standard of care group at the ratio of 1:1
| Arm | Type | Receives |
|---|---|---|
| M+K group | Experimental | Drug: Methadone, Drug: ketamineParticipants in this arm will receive the intervention with methadone and ketamine |
| SOC group | Active comparator | Drug: Hydromorphone, Drug: fentanylParticipants in this arm will receive the standard of care with combination of hydromorphone and fentanyl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneParticipants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation | Drug | M+K group |
| ketamineParticipants in this group will receive one bolus dose of intravenous Methadone and Ketamine at the start of operation | Drug | M+K group |
| HydromorphoneParticipants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure | Drug | SOC group |
| fentanylParticipants in this group will receive standard of care for pain with either intravenous fentanyl and/or hydromorphone boluses during the procedure | Drug | SOC group |
Primary outcome
Postoperative Pain
Time frame: 8, 16, 24, 32, 40 and 48hours post-surgery finish
postoperative opioid consumption (measured as morphine milligram equivalents ((MME)) 48 hours after surgery
Postoperative Pain
Time frame: 8, 16, 24, 32, 40 and 48hours post-surgery finish
Subjective postoperative pain scores measured as 0-10 (10 being the worst pain)
8 secondary outcomes
Length of stay in intensive care unit
Time frame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Length of stay in hospital
Time frame: Post surgery finish until discharge from hospital, or date of death from any cause, whichever came first, assessed up to 30 days
Delirium
Time frame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Respiratory complications
Time frame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Narcotics reversal agent
Time frame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Postoperative adjunct pain modalities
Time frame: Post surgery finish until discharge from intensive care unit, or date of death from any cause, whichever came first, assessed up to 30 days
Correlation Between Study Drug Exposure and Early Post-Transplant Laboratory Markers of Liver Dysfunction
Time frame: Immediate to 24hrs post surgery finish
Correlation Between Donor and Surgical Factors and Postoperative Opioid Use (MME)
Time frame: From the end of surgery through 48hr post surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Individual participant dataSharing planned: No. Sensitive transplant data will not be shared for patients privacy
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Nazemian, MD, PhD principal investigator
Lahey Clinic, Department of Anesthesiology, Perioperative and Pain Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone, ketamine and Hydromorphone in people with Liver Transplantation, run by Lahey Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative Pain (time frame: 8, 16, 24, 32, 40 and 48hours post-surgery finish). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.