Liver TransplantationNCT04023773
Sequential Hypo- and Normo-thermic Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
A study testing Liver Machine Perfusion (MP) device in people with Liver Transplantation, run by Koji Hashimoto at 1 site in United States.
Trial summary
Hypothermic machine perfusion (HMP) has been shown to be beneficial to preserve extended criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) had the same benefits and also the convenience on liver quality assessment. 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?
- Liver Machine Perfusion (MP) device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2021to 30 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Patients undergoing liver transplantation
- Age 18 or older at the time of transplantation
- Willingness and ability to comply with the study procedures
- Signed Informed Consent Form
Who cannot join
- Recipient of partial grafts (split and living donors)
- Mentally or legally incapacitated subjects
- Inability to understand the procedures due to language barriers
- Multiorgan transplant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assess Safety and Feasibility of Sequential Hypothermic Oxygenated Machine Perfusion and Normothermic Machine Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
Hypothermic machine perfusion (HMP) has been shown to be beneficial to preserve extended criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) had the same benefits and also the convenience on liver quality assessment. The investigators proposed to do sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers by using an institutional-developed perfusion device for liver transplantation.
Read the detailed description
Liver transplantation is a successful therapy on the patients with end-stage liver disease, however is limited by the shortage of donor organs. Donor criteria were expanded in the past decades, however the extended criteria donor (ECD) livers may induce a higher risk of complications. Static cold storage (SCS) is the standard procedure for ex vivo liver preservation for about 4 decades, but has the limitation on preserving ECD livers and especially the inconvenience to evaluate liver quality prior to transplantation. Hypothermic (4-8 Celsius degree) machine perfusion (HMP) and Normothermic (35-37 Celsius degree) machine perfusion (NMP) have been shown to be beneficial to preserve extended criteria donor (ECD) livers respectively. NMP also had the convenience on liver quality assessment. The investigators had an institutional-developed device for liver NMP used on 25 patients with the FDA's IDE approval. In the present study the investigators are proposing to expand the use of the device on sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers. This will be a single center prospective pilot study. The liver metabolism and hydrodynamics during perfusion will be recorded. The transplant procedure and post-transplant care will follow the clinical standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of patient survival and primary non function (PNF) within 30 days after transplantation, while the secondary end points will be: Early Allograft Dysfunction (EAD), 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on "on-pump" viability markers, and the incidence of adverse effect (AE).
- Conditions
- Liver Transplantation
- Being tested
- Liver Machine Perfusion (MP) device
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liver Machine Perfusion (MP) deviceDevice
Donor livers will have ex vivo continuous perfusion on the institutional-developed Liver MP device. The temperature of liver grafts will be controlled during perfusion.
| Study group | Role | What they receive |
|---|---|---|
| Liver perfusion | Experimental | Device: Liver Machine Perfusion (MP) Device
The liver grafts will be preserved at hypothermic and normothermic temperature on the institutional-developed Liver MP Device, and have continuous perfusion with oxygen supply in the ex vivo organ preservation phase. Receives: Device: Liver Machine Perfusion (MP) device |
What is being measured
The primary outcome is the main question the study is designed to answer.
patient survival at 1 month post-transplant
Patient survival will be recorded at 1 month post transplantation.
Measured: 1 month post-transplant
graft survival at 1 month post-transplant
graft survival will be recorded at 1 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death.
Measured: 1 month post-transplant
Secondary outcomes (10)
rate of post-transplant early allograft dysfunction (EAD)
EAD is defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin ≥10mg/dL on post-operative day (POD) 7, international normalized ratio (INR) ≥1.6 on POD 7, and alanine or aspartate aminotransferases (ALT or AST) >2000 IU/L within the first 7 days.
Measured: in the first 7 days after transplantation
patient survival at 6 month post-transplant
patient survival will be recorded at 6 months post transplantation.
Measured: 6 month post-transplant
graft survival at 6 month post-transplant
graft survival will be recorded at 6 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death.
Measured: 6 month post-transplant
Estimated blood loss at transplant surgery
Estimated blood loss (ml) during transplant surgery
Measured: during surgery
peak alanine aminotransferases in the first 7 days after transplantation
peak level (U/L) of alanine aminotransferases in the first 7 days after transplantation
Measured: in the first 7 days after transplantation
peak aspartate aminotransferases in the first 7 days after transplantation
peak level (U/L) of aspartate aminotransferases in the first 7 days after transplantation
Measured: in the first 7 days after transplantation
total bilirubin on post-operative day 7
total bilirubin (mg/dL) on post-operative day 7
Measured: on post-operative day 7
international normalized ratio on post-operative day 7
international normalized ratio on post-operative day 7
Measured: on post-operative day 7
Hospital length of stay
Length of stay (days) in the hospital at the time for transplantation
Measured: up to 36 weeks
ICU length of stay
Length of stay (days) in ICU at the time after liver transplantation
Measured: up to 36weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2019
- Study start1 May 2021
- Primary completion1 Jan 2026 (estimated)
- Study completion30 Jan 2027 (estimated)
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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Eighteen extended criteria donor livers will be transplanted after receiving sequential hypothermic and normothermic machine perfusion preservation prior to transplantation.
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Koji Hashimoto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Koji Hashimoto, The Cleveland Clinic
- Investigators
- Koji Hashimoto, MD, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04023773
- Sponsor's protocol ID
- Sequential perfusion
- Status last verified
- Jul 2024
- First submitted
- 10 Jul 2019
- Last updated
- 26 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assess Safety and Feasibility of Sequential Hypothermic Oxygenated Machine Perfusion and Normothermic Machine Perfusion to Preserve Extended Criteria Donor Livers for Transplantation
- ClinicalTrials.gov ID
- NCT04023773
- Acronym / sponsor ID
- Sequential perfusion
- Conditions
- Liver Transplantation
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Koji HashimotoUniversity, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 18 Jul 2019 (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.
Hypothermic machine perfusion (HMP) has been shown to be beneficial to preserve extended criteria donor (ECD) livers for transplantation. Normothermic machine perfusion (NMP) had the same benefits and also the convenience on liver quality assessment. The investigators proposed to do sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers by using an institutional-developed perfusion device for liver transplantation.
Detailed description
Liver transplantation is a successful therapy on the patients with end-stage liver disease, however is limited by the shortage of donor organs. Donor criteria were expanded in the past decades, however the extended criteria donor (ECD) livers may induce a higher risk of complications. Static cold storage (SCS) is the standard procedure for ex vivo liver preservation for about 4 decades, but has the limitation on preserving ECD livers and especially the inconvenience to evaluate liver quality prior to transplantation. Hypothermic (4-8 Celsius degree) machine perfusion (HMP) and Normothermic (35-37 Celsius degree) machine perfusion (NMP) have been shown to be beneficial to preserve extended criteria donor (ECD) livers respectively. NMP also had the convenience on liver quality assessment. The investigators had an institutional-developed device for liver NMP used on 25 patients with the FDA's IDE approval. In the present study the investigators are proposing to expand the use of the device on sequential HMP (1-4 hours) and NMP (1-14 hours) on 18 ECD transplanted human livers. This will be a single center prospective pilot study. The liver metabolism and hydrodynamics during perfusion will be recorded. The transplant procedure and post-transplant care will follow the clinical standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of patient survival and primary non function (PNF) within 30 days after transplantation, while the secondary end points will be: Early Allograft Dysfunction (EAD), 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on "on-pump" viability markers, and the incidence of adverse effect (AE).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Eighteen extended criteria donor livers will be transplanted after receiving sequential hypothermic and normothermic machine perfusion preservation prior to transplantation.
| Arm | Type | Receives |
|---|---|---|
| Liver perfusion | Experimental | Device: Liver Machine Perfusion (MP) deviceDevice: Liver Machine Perfusion (MP) Device The liver grafts will be preserved at hypothermic and normothermic temperature on the institutional-developed Liver MP Device, and have continuous perfusion with oxygen supply in the ex vivo organ preservation phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients undergoing liver transplantation
- Age 18 or older at the time of transplantation
- Willingness and ability to comply with the study procedures
- Signed Informed Consent Form
Key exclusion criteria (4 listed)
- Recipient of partial grafts (split and living donors)
- Mentally or legally incapacitated subjects
- Inability to understand the procedures due to language barriers
- Multiorgan transplant
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 |
|---|---|---|
| Liver Machine Perfusion (MP) deviceDonor livers will have ex vivo continuous perfusion on the institutional-developed Liver MP device. The temperature of liver grafts will be controlled during perfusion. | Device | Liver perfusion |
Primary outcome
patient survival at 1 month post-transplant
Time frame: 1 month post-transplant
Patient survival will be recorded at 1 month post transplantation.
graft survival at 1 month post-transplant
Time frame: 1 month post-transplant
graft survival will be recorded at 1 month post transplantation. The allograft will be considered lost if a patient has a primary non function (PNF), liver re-transplant or in the event of patient death.
10 secondary outcomes
rate of post-transplant early allograft dysfunction (EAD)
Time frame: in the first 7 days after transplantation
patient survival at 6 month post-transplant
Time frame: 6 month post-transplant
graft survival at 6 month post-transplant
Time frame: 6 month post-transplant
Estimated blood loss at transplant surgery
Time frame: during surgery
peak alanine aminotransferases in the first 7 days after transplantation
Time frame: in the first 7 days after transplantation
peak aspartate aminotransferases in the first 7 days after transplantation
Time frame: in the first 7 days after transplantation
total bilirubin on post-operative day 7
Time frame: on post-operative day 7
international normalized ratio on post-operative day 7
Time frame: on post-operative day 7
Hospital length of stay
Time frame: up to 36 weeks
ICU length of stay
Time frame: up to 36weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
- Individual participant dataSharing planned: No
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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.
Koji Hashimoto, MD, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liver Machine Perfusion (MP) device in people with Liver Transplantation, run by Koji Hashimoto at 1 site 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 4 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
patient survival at 1 month post-transplant (time frame: 1 month post-transplant). 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 26 Jul 2024.