Objective of this study is to compare 1-year garft survival after hypothemic machine perfusion with oxygentaed perfusion solution versus static cold storage of extended criteria kidneys from DBD donors.
ID
Source
Brief title
Condition
- Nephropathies
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome for this study is Graft survival at 12 months after
transplantation.
Secondary outcome
- Patient and (death censored) graft survival at day 7, 3, 6 and 12 months
after transplantation. eGFR defined by the MDRD equation at day 7, 3, 6 and 12
months after transplantation.
- Delayed graft function defined as the need for dialysis in the first 7 days
after transplantation and preceding the return of kidney function.
- Slow graft function based on functional DGF defined as the absence of
decrease in the serum creatinine level of at least 10% per day for at least 3
consecutive days in the first 7 days after transplantation.
- Primary non-function defined as the continued need for dialysis at 3 months
after transplantation.
- Comparison of biopsy proven acute rejection between the 2 groups.
- Quality of life measures (EQ-5D-5L) at consent, 3 and 12 months, length of
hospital stay (including ICU) and need/length for dialysis treatment
Background summary
Renal transplantation remains the therapy of choice for patients with end stage
renal disease. However, the number of patients waiting for a kidney graft
continues to increase and far exceeds the availability of donor grafts (1-3). A
large number of deceased organ transplants manifest a degree of early
dysfunction leading to the clinical syndrome of Delayed Graft Function (DGF)
(4,5). DGF represents a significant problem in clinical kidney transplantation
affecting up to 30% of all deceased donor graft recipients (6). This has an
impact on short-term management, including the requirement of hemodialysis
treatment and is associated with an increased risk of acute rejection. Moreover
DGF has been shown in multivariate analyses to increase the incidence of
chronic nephropathy and later graft loss (4). The shortage of donor organs has
led the transplant community to accept an increasing number of older and more
marginal donor grafts for transplantation (7). Kidneys from these donors are
particularly vulnerable for the development of DGF and have decreased long term
graft survival. One important modifiable risk factor of DGF is ischemia injury
sustained during organ preservation. Optimizing the preservation of grafts
during the preservation phase is essential to reduce this ischemic injury. In
those older and more marginal donor kidneys, an optimized preservation is
therefore of even greater importance.
Study objective
Objective of this study is to compare 1-year garft survival after hypothemic
machine perfusion with oxygentaed perfusion solution versus static cold storage
of extended criteria kidneys from DBD donors.
Study design
The study will be conducted as a prospective, randomized, parallel group,
single blinded, controlled, multi-centre, non-paired superiority trial;
allocation will be on a 1:1 basis and an intention-to-treat method will be used
to analyze the results.
After accepting the potential ECD organ for donation, kidneys will be allocated
following the standard Eurotransplant/ UK-transplant allocation rules.
In a non-paired-design, each ECD kidney that has been accepted for
transplantation by one of the participating centres will be randomly assigned
to SCS or to SCS followed by reconditioning by end-ischemic oxygenated HMP
(HRMP+O2). Randomizing kidneys after they have been accepted for
transplantation avoids a potential bias that acceptance of the kidney is being
influenced by the preservation modality.
If two kidneys are accepted for transplantation by the same centre the surgeon
will decide which kidney to transplant first according to their local protocol.
It is not essential for both kidneys from a donor to enter the trial. If only
one of the kidneys is deemed transplantable, it can still be included in the
trial analysis.
Exceptionally anatomical situations may not allow connection of a kidney to the
perfusion circuit. In this situation the kidney should be preserved by cold
storage alone even though it was randomized to HRMP+O2.
Intervention
Intervention is oxygenated hypothermic machine perfusion while the controlgroup
excists of kidney that have been preserved by static cold storage.
Study burden and risks
Since the intervention occurs prior to kidney transplantation, there are no
study specific changes to the standard follo-up care. Also, there are no
additional strategies, outside general measures to ensure regular recipient
follow-up, for monitoring and improving adherence necessary. For the recipient,
no changes will be made considering standard care, with the exception of taking
additional bloodsamples during transplantation. A minimal burden and risk for
the participants included in this study. The risk associated with participation
is that the oxygenation at the time of machine perfusion could have an harmfull
effect on the future function of the graft. During a large animaltrial on pigs
the later function of the graft was better after oxygenated machine perfusion.
There is a minimal burden an a small risk for the participants included in this
study.
Churchill Hospital, Old Road, Headington 1
Oxford OX3 7LE
GB
Churchill Hospital, Old Road, Headington 1
Oxford OX3 7LE
GB
Listed location countries
Age
Inclusion criteria
For the donor and the donated kidney:
- All kidneys from DBD donors (Donation after BrainDeath) fulfilling the UNOS-ECD criteria; donors aged 60 years or older, or donors aged 50 years or older with two of the following riskfactors: hypertension. terminal creatinin >1,5mg/dL or a cerebral vascular cause of death.;For the recipient of the donated kidney:
- Aged 18 years or older
- Listed for renal transplantation due to end stage renal disease on the ET or NHSBT renal waiting list within one of the participating centers.
- Participant is willing to participate in the study and has provided written informed consent.
- This transplantation is the participant's first or re-transplantation.
Exclusion criteria
For the donor and the donated kidney:
- Kidneys used for a multi-organ transplant procedure.
- Kidneys from standard criteria donors (SCD).
- Kidneys procured from a DCD donor (Donation after Circulatory Death).
- Kidneys used for a double kidney transplant within the same recipient.
- Kidneys procured from donors older than 85 years.;For the recipient:
- Simultaneous participation in another perfusion trial.
- Scheduled to undergo multi-organ transplantation.
- Planned dual-kidney transplantation.
- Is unable or unwilling to provide informed consent.
- If the kidney is judged to be not transplantable.
- Simultaneous participation in another perfusion trial.
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 |
|---|---|
| ISRCTN | ISRCTN63852508 |
| CCMO | NL49912.042.14 |