Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT01384006 |
| Other study ID # |
EXPAND |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
June 27, 2011 |
| Last updated |
June 30, 2011 |
| Start date |
June 2011 |
| Est. completion date |
June 2014 |
Study information
| Verified date |
June 2011 |
| Source |
University of Regensburg |
| Contact |
Stefan A Farkas, MD |
| Phone |
+49-941-944 |
| Email |
stefan.farkas[@]klinik.uni-r.de |
| Is FDA regulated |
No |
| Health authority |
Germany: Ethics Commission |
| Study type |
Observational
|
Clinical Trial Summary
To expand the donor pool for pancreas allografts. For detailed description please see below.
Description:
This is an investigator initiated prospective, non-randomized feasibility-study, comparing
recipients of EDC-pancreas allografts (SPK or PTA) with patients undergoing SPK or PTA with
standard criteria allografts.
Simultaneous Pancreas Kidney transplantation (SPK) or Pancreas Transplantation alone (PTA)
are life saving procedures for patients with type 1 (juvenile) diabetes mellitus and
impaired renal function. Although the waiting lists for SPK and PTA are increasing, the
numbers of pancreas transplantations are declining in the Eurotransplant (ET) area
(www.eurotransplant.nl). One major reason for this decline is the fact that a large number
of pancreas allografts, potentially eligible for transplantation are excluded by the ET
pancreas allocation system (EPAS). Those criteria include an organ-specific cut-off for
donor age >50 years and/or BMI>30. This means that donors that are older than 50 years or
donors with a BMI >30 are, at the moment, not considered for solid organ transplantation.
The pancreas will be directly allocated for islet transplantation (Eurotransplant manual -
version may 26, 2009).
The organ-specific cut-off was once established to provide donor pancreases for islet
transplantation. Although 173 pancreases were allocated and retrieved for islet
transplantation only 17 islet transplantations were performed in the whole ET area in 2008
(ET data). In Germany two islet transplantations were performed in 2009. Best results after
islet transplantation are achieved with organs obtained from young obese donors. Concerning
allocation, no conflict of interest exists between whole organ and islet transplantation,
the single active German islet center will take part in the EXPAND study. Meanwhile,
according to the suggestions by the EXPAND study group, extended donor pancreases are
intended to be offered regionally as "rescue" allocation to the centers. The centers should
then decide if this organ can be transplanted as whole organ or if it can be used for
islets.
As the average age for a post mortal organ donor in the ET area is now 58 years, there is a
severe donor selection by age leading to organ shortage. In Germany in 2008 the total number
of organ donors was 1.198. However, only 510 donors had an age between 3 and 50 years and
thus were potentially eligible for pancreas donation. Out of the 510 donors only 183
pancreases (36% of all potential, age restricted pancreas donors) were retrieved and 127
(25%) were transplanted (DSO, Deutsche Stiftung für Organtransplantation e.V.). Altogether,
676 donors were not even screened for pancreas donation due to age, regardless to all other
medical conditions. In addition, approximately 13% were not eligible for pancreas donation
only due to BMI. Moreover, in the ET-area pancreases are allocated without local priority
leading to longer ischemic times due to transport ways. However, there are data from other
allocation areas throughout the world (UNOS or UK) showing that a good overall outcome after
PTx can be achieved with donors exceeding the defined allocation criteria defined by ET
(older than 50 or BMI>30), if the cold ischemic time is kept short. In Great Britain, a
local retrieval and allocation system was installed in 2000 resulting in a steep increase in
pancreas transplantation. Moreover, within this new allocation system the currently
worldwide largest and most successful pancreas transplant program was initiated in Oxford in
2004 with an extensive use of extended pancreas donors leading to excellent results. These
extended criteria avoided donor BMI restriction, and accepted donors with an age between 8
and 68 years. Meanwhile 350 SPK and PTA were transplanted with an excellent one year
pancreas survival of 91%, kidney survival 95% and a patient survival of 96%.
In the US, a retrospective analysis of OPTN registries compared 8.850 SPK from young donors
vs. 776 SPK from donors >45 years. It showed that patients transplanted from an older donor
have equal survival compared to those who were waiting for a young donor for more than 1.5
years. However the earlier transplanted patient is instantly off dialysis and insulin. Good
results were already achieved with extended pancreas donors in the US and also in one German
study.
Based on those findings, a new pancreas allocation system was established in the USA where
standard pancreases (donor age < 50y or BMI < 30) are allocated first on local, then on
regional and then on national levels and extended pancreas (donor age > 50 years or BMI >
30) are allocated locally only.
In conclusion, these data indicate the requirement for a new allocation system also in the
ET area to be able to provide a sufficient number of organs for patients on the waiting
list. We therefore suggest a new pancreas allocation system where donors with an age of
50-60 years or a BMI of 30-34 are allocated regionally within a cold ischemic time < 12 h.
To prove the hypothesis that extended pancreas allograft donors can be used safely with
equal outcome in recipients a prospective comparative multicenter feasibility-study is
required.
A good example of a successful change of allocation rules is the European Senior Donor
Program (ESDP) for kidneys, the so called "old for old" program. Within this program kidneys
from donors >65 years are allocated regionally to patients >65 years with a relatively short
ischemic time without HLA matching. For this purpose a comparative study was performed to
prove the efficacy of this allocation change.
The standard immunosuppression for SPK or PTA includes induction therapy with antibodies.
Maintenance therapy is mostly performed with a tacrolimus / mycophenolate mofetil
combination. The usage of calcineurin inhibitors for maintenance therapy is characterized by
a clear transition from cyclosporine to tacrolimus. Myfortic® vs. Cell Cept® shows
beneficial effects after SPK in a large single center comparison. Corticosteroids are
administered to the majority of patients; however, steroid-avoidance and steroid-withdrawal
protocols are increasingly common.
