To study the feasibility, and reliability of ex-situ viability testing of high risk donor livers using DHOPE, rewarming and NMP, by assessing graft survival at 3 months after transplantation.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is graft survival at 3 months after transplantation.
Secondary outcome
Secondary study parameters:
- Graft and patient survival at 7 days and 1 month.
- Primary non-function (PNF): Occurrence of retransplantation or patient death
within the first 7 days after OLT, without any identifiable cause of graft
dysfunction(12).
- Early allograft dysfunction (EAD), presence of one or more of the following
variables (13):
o Elevation of AST and/or ALT above a defined cut-off value (>2000 IU/mL )
within the first 7 days after OLT;
o Elevated international normalized ratio (INR) of *1.6 on day 7 after OLT;
o Elevated bilirubin levels of *10 mg/dL on day 7 after OLT.
- Development of non-anastomotic biliary strictures (NAS).
- Biochemical analysis of graft function and ischemia-reperfusion injury
determined with serum levels of ALT, AST, AlkP, *GT, INR, lactate, creatinine,
platelets and total bilirubin at postoperative day 0-7 and 1 and 3 months.
Background summary
Currently, there is a shortage of suitable donor livers. To expand the donor
pool, livers from high risk donors, or otherwise termed extended criteria donor
(ECD) livers are increasingly accepted. ECD livers carry an increased risk of
developing severe complications. Machine perfusion is a promising technique in
predicting whether an ECD liver is susceptible to developing one of these
complications or not, prior to transplantation. Normothermic machine perfusion
(NMP) is conducted at a physiologic temperature of 37 °C, using a perfusion
fluid based on an oxygen carrier. This results in a metabolically active liver,
offering the ability to assess liver function and viability ex-situ. Aside from
NMP, dual hypothermic oxygenated machine perfusion (DHOPE), conducted at 4 -
14°C, is advocated to improve the quality of ECD livers. Hence, this protocol
is designed to assess viability of high risk donor livers using NMP, prior to
transplantation. DHOPE, being superior in optimizing the quality of ECD livers
will be conducted before gradually rewarming the donor liver to a normothermic
temperature. During NMP a viability assessment will be carried out. Thus, high
risk donor livers that would previously not have been accepted for
transplantation, will be transplanted when meeting the viability criteria.
Therefore, the donor pool might be expanded.
Study objective
To study the feasibility, and reliability of ex-situ viability testing of high
risk donor livers using DHOPE, rewarming and NMP, by assessing graft survival
at 3 months after transplantation.
Study design
A single center phase-I clinical trial, in which 10 liver transplants will be
included based on empirical experience.
Intervention
Each high risk donor liver accepted for this study will undergo machine
perfusion. First, DHOPE will take place, before gradually rewarming the liver
till a normothermic temperature. Secondly, after rewarming, NMP will take
place.
Study burden and risks
The risks and the burden associated with this study will be limited. If a high
risk donor liver is not viable or *poor-functioning* at the moment of viability
assessment, the liver will not be transplanted, in order to protect the
recipient. Moreover, if there is a device error * disadvantageous for the donor
liver * the liver will neither be transplanted. The only drawback concerning
this is the fact that the patient will come to the hospital unnecessarily. The
advantage is that when a liver is being transplanted the odds are quite high
that the liver is of very reasonable quality. Least the liver will be perfused
with Hemopure ®, an oxygen carrier. Despite of many studies, Hemopure ® is not
yet approved in the Netherlands. However, based on the information on Hemopure
®, as described in this protocol and in the Investigators Brochure, there is no
reason to believe that Hemopure ® causes significant damage.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:;Recipient
- Adult patients (* 18 years old)
- Given informed consent ;Donor grafts
- Donors with a body weight *40 kg
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:;Recipient
- Simultaneous participation in another clinical trial that might possibly influence this trial
- Mental conditions rendering the subject incapable to understand the nature, scope and consequences of the trial
- Listed for liver transplantation due to fulminant liver failure or retransplantation because of PNF
- Recipient positive test for HIV
- Allergic to one of the components in the perfusion fluid. ;Donor grafts
- Donor positive for HIV, Hepatitis B or C
- Split or partial liver grafts
- Domino donor livers
- Expected cold ischemia time of * 10 hours
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL58015.042.16 |
| Other | TC=5972 |