Liver TransplantationNCT02515708
Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
A study testing Normothermic Liver perfusion Device in people with Liver Transplantation, run by Cristiano Quintini at 1 site in United States.
Trial summary
Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Normothermic Liver perfusion Device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2016to 9 Jun 2020
- Phase
- Interventional
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing primary liver transplantation
- Age 18-75 years at the time of transplantation
- Willingness and ability to comply with the study procedures
- Signed Informed Consent Form
- For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria.
Who cannot join
- Recipient Exclusion Criteria:
- History of prior solid organ transplantation
- Patient on a respiratory and/or cardiocirculatory support at the time of transplant
- MELD score >35
- HIV positive patient
- Patient with current severe systemic infection
Show all 14Show fewer
- Multiorgan transplant
- Donor Exclusion Criteria:
- Donor age <14 or >70 years
- Liver steatosis (on visual estimate or on liver biopsy) > 30%
- Donors with Grade 2-3 traumatic liver laceration
- Partial grafts (living donors and split liver donors)
- Liver in which the investigator is unwilling or unable (for logistical reasons) to perform normothermic machine perfusion (NMP) preservation
- Inability to NMP perfuse the liver within 4 hours after cross clamp
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Thirty-two livers with acceptable quality for transplantation will be preserved with NMP in 2-18 hours and transplanted. The follow-up period will be 6 months post-transplantation. The outcome will be compared to 100 historical patients transplanted in our program in the past 5 years (liver preserved using CS) with matched characteristics on age, Model for End-Stage Liver Disease (MELD) score, preservation time, etc.
Read the detailed description
The shortage of donor organs leads to the use of marginal donors including donors after cardiac death. Normothermic machine perfusion (NMP) preservation is a promising method to decrease their high risk of complication compared to the standard cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation.
This will be a single center prospective cohort pilot study. Thirty-two livers that have acceptable quality for transplantation will be preserved with NMP in 2-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at physiological temperature and have oxygen and nutrient supply with continuous perfusion. The transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of post-transplant Early Allograft Dysfunction (EAD), while the secondary end points will be: primary non function (PNF) rate, 1 and 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, intraoperative hepatic arterial and portal flow measurement, rate and magnitude of post-reperfusion syndrome, 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).
The outcome will be compared to a control group of 100 historical patients (matched with a 1:4 ratio) transplanted in our program in the past 10 years (liver preserved using CS). Control subjects will be matched using donor and recipient age, Model for End-Stage Liver Disease (MELD) score, cold ischemia time, donor risk index and presence of steatosis.
- Conditions
- Liver Transplantation
- Being tested
- Normothermic Liver perfusion Device
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normothermic Liver perfusion DeviceDevice
The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.
| Study group | Role | What they receive |
|---|---|---|
| Normothermic Liver perfusion | Experimental | This group has the liver grafts preserved using the Normothermic Liver perfusion Device. Receives: Device: Normothermic Liver perfusion Device |
| Normothermic Machine Perfusion (single pump) | Other | This group has the liver grafts preserved using a single-pump variant of the Normothermic Liver perfusion Device. Receives: Device: Normothermic Liver perfusion Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers
The presence of at least one of the following at post-transplant 7 days: serum bilirubin >= 10 mg/dL, international normalized ratio (INF) >= 1.6; and/or aspartate aminotransferase (AST) > 2000 U/L at any time in the first 7 post-transplant days (POD)
Measured: 7 days post-transplantation
Secondary outcomes (15)
primary non-function rate
Measured: in the first 10 days post-transplantation
graft survival
The allograft will be considered lost if a patient has a liver re-transplant or in the event of patient death.
Measured: 6 months post-transplantation
peak liver function tests in the first 7 days post-transplantation
Measured: in the first 7 days post-transplantation
intraoperative flow measurement
Flows will be measured with a transit time flowmeter (VeriQ system, MediStim A/S, Oslo, Norway) after graft reperfusion. The following parameters will be recorded as per our standard practice during liver transplantation: portal venous flow, hepatic artery flow, and hepatic artery flow after temporary portal vein occlusion.
Measured: intraoperative
post reperfusion syndrome (composite)
rate and magnitude
Measured: in the first 7 days post-transplantation
surgical outcomes (composite)
operative time, transfusion requirement
Measured: intraoperative
rate of post-transplant kidney failure
Measured: in the 1, 3, 6 ,9 months post-transplantation
histology of liver parenchyma
Measured: On the day of transplantation
vascular complications rate
Measured: in the first day post-transplantation
biliary complications rate
Measured: 6 months post-transplantation
hospital and ICU length of stay (composite)
Measured: 6 months post-transplantation
rejection rate
Measured: 6 months post-transplantation
opportunistic viral infection rate
Measured: 6 months post-transplantation
patient survival
Measured: 6 months post-transplantation
histology of bile duct
Measured: On the day of transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2015 (estimated)
- Study start16 May 2016
- Primary completion9 Jun 2020
- Study completion9 Jun 2020
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cristiano Quintini
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Cristiano Quintini, The Cleveland Clinic
- Investigators
- Cristiano Quintini, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02515708
- Sponsor's protocol ID
- 15-549
- Status last verified
- Oct 2020
- First submitted
- 30 Jul 2015
- Last updated
- 19 Oct 2020
- 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 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
- ClinicalTrials.gov ID
- NCT02515708
- Acronym / sponsor ID
- 15-549
- Conditions
- Liver Transplantation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Cristiano QuintiniUniversity, hospital or other
- Study start
- 16 May 2016 (actual)
- Primary completion
- 9 Jun 2020 (actual)
- Study completion
- 9 Jun 2020 (actual)
- First posted
- 5 Aug 2015 (estimated)
- 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.
Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Thirty-two livers with acceptable quality for transplantation will be preserved with NMP in 2-18 hours and transplanted. The follow-up period will be 6 months post-transplantation. The outcome will be compared to 100 historical patients transplanted in our program in the past 5 years (liver preserved using CS) with matched characteristics on age, Model for End-Stage Liver Disease (MELD) score, preservation time, etc.
Detailed description
The shortage of donor organs leads to the use of marginal donors including donors after cardiac death. Normothermic machine perfusion (NMP) preservation is a promising method to decrease their high risk of complication compared to the standard cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation.
This will be a single center prospective cohort pilot study. Thirty-two livers that have acceptable quality for transplantation will be preserved with NMP in 2-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at physiological temperature and have oxygen and nutrient supply with continuous perfusion. The transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of post-transplant Early Allograft Dysfunction (EAD), while the secondary end points will be: primary non function (PNF) rate, 1 and 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, intraoperative hepatic arterial and portal flow measurement, rate and magnitude of post-reperfusion syndrome, 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).
The outcome will be compared to a control group of 100 historical patients (matched with a 1:4 ratio) transplanted in our program in the past 10 years (liver preserved using CS). Control subjects will be matched using donor and recipient age, Model for End-Stage Liver Disease (MELD) score, cold ischemia time, donor risk index and presence of steatosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normothermic Liver perfusion | Experimental | Device: Normothermic Liver perfusion DeviceThis group has the liver grafts preserved using the Normothermic Liver perfusion Device. |
| Normothermic Machine Perfusion (single pump) | Other | Device: Normothermic Liver perfusion DeviceThis group has the liver grafts preserved using a single-pump variant of the Normothermic Liver perfusion Device. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing primary liver transplantation
- Age 18-75 years at the time of transplantation
- Willingness and ability to comply with the study procedures
- Signed Informed Consent Form
- For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria.
Key exclusion criteria (14 listed)
- History of prior solid organ transplantation
- Patient on a respiratory and/or cardiocirculatory support at the time of transplant
- MELD score >35
- HIV positive patient
- Patient with current severe systemic infection
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 |
|---|---|---|
| Normothermic Liver perfusion DeviceThe liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase. | Device | Normothermic Liver perfusion, Normothermic Machine Perfusion (single pump) |
Primary outcome
the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers
Time frame: 7 days post-transplantation
The presence of at least one of the following at post-transplant 7 days: serum bilirubin >= 10 mg/dL, international normalized ratio (INF) >= 1.6; and/or aspartate aminotransferase (AST) > 2000 U/L at any time in the first 7 post-transplant days (POD)
15 secondary outcomes
primary non-function rate
Time frame: in the first 10 days post-transplantation
graft survival
Time frame: 6 months post-transplantation
peak liver function tests in the first 7 days post-transplantation
Time frame: in the first 7 days post-transplantation
intraoperative flow measurement
Time frame: intraoperative
post reperfusion syndrome (composite)
Time frame: in the first 7 days post-transplantation
surgical outcomes (composite)
Time frame: intraoperative
rate of post-transplant kidney failure
Time frame: in the 1, 3, 6 ,9 months post-transplantation
histology of liver parenchyma
Time frame: On the day of transplantation
vascular complications rate
Time frame: in the first day post-transplantation
biliary complications rate
Time frame: 6 months post-transplantation
hospital and ICU length of stay (composite)
Time frame: 6 months post-transplantation
rejection rate
Time frame: 6 months post-transplantation
opportunistic viral infection rate
Time frame: 6 months post-transplantation
patient survival
Time frame: 6 months post-transplantation
histology of bile duct
Time frame: On the day of transplantation
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 19 Oct 2020.
- 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.
Cristiano Quintini, MD 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 Normothermic Liver perfusion Device in people with Liver Transplantation, run by Cristiano Quintini 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 5 inclusion and 14 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 19 Oct 2020. 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?
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?
the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers (time frame: 7 days post-transplantation). 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 19 Oct 2020.