Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02911714 |
| Other study ID # |
IRB_00092223 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
February 21, 2018 |
| Est. completion date |
June 30, 2022 |
Study information
| Verified date |
June 2024 |
| Source |
University of Utah |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Contrast-enhanced ultrasound (CEUS) is a promising non-invasive imaging tool that may aid in
the early detection of kidney transplant complications, such as delayed graft function (DGF)
and acute allograft rejection. The technique uses an intravenous contrast agent to improve
organ visualization with standard duplex ultrasound equipment. A number of FDA-approved
agents, including Optison, Definity and Lumason are widely used to improve visualization in
technically limited echocardiograms, and Lumason was recently approved for contrast-enhanced
ultrasound of the liver. The specific aims of this study are to: develop, implement and
refine a contrast-enhanced ultrasound protocol using Lumason to safely maximize kidney
allograft visualization; determine associations between contrast-enhanced ultrasound and
patterns of allograft injury consistent with delayed graft function; and to compare
contrast-enhanced ultrasound with duplex ultrasound for differentiating acute rejection from
other causes of dysfunction.
Description:
Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD) given
improved quality of life, longer survival and lower costs compared with chronic dialysis.
Despite these long-term benefits, the first year post-transplant is a critical period that
influences health care costs for transplantation and long-term patient and allograft
survival. The two most common complications in the first year are delayed graft function
(DGF), which affects nearly 25% of deceased-donor transplants, and acute allograft rejection,
which affects nearly 10% of all transplants (deceased and living donor). DGF is most commonly
caused by severe ischemia-reperfusion injury at transplantation and is a known risk factor
for acute rejection and premature failure. Driven by an ever-growing transplant waiting list
and limited organs, efforts to utilize higher-risk kidneys for increasingly higher-risk
recipients may further increase these complication rates. While treatments exist for DGF and
acute rejection, the current diagnostic paradigm is to obtain a duplex ultrasound (DUS) of
the allograft, based on serial changes in serum creatinine, and then proceed to biopsy if
there is clinical concern for rejection. Biopsy is the gold standard to differentiate between
causes of allograft dysfunction, but the procedure is invasive and typically takes 24 hours
or longer for an interpretation. Thus, early detection of these complications using
non-invasive diagnostic methods (a major transplant research goal) could reduce our reliance
on biopsies and help improve long-term patient and allograft survival.
Researchers in the United States have safely performed contrast-enhanced ultrasounds of the
kidney in healthy participants, and radiologists have used ultrasound contrast agents
off-label to better visualize organs other than the heart when clinically indicated. In terms
of kidney transplants, European data suggest CEUS of the allograft on post-operative day
(POD) 7 is superior to DUS for predicting 12-month allograft function, but there are no
published studies using CEUS on POD 1 to diagnose DGF or acute rejection.
The pathophysiology of both DGF and acute rejection involve interactions between the
microvasculature, parenchymal cells and inflammatory cells, though with differences in timing
and within different zones of the kidney itself. A very important feature of CEUS is its
capacity to measure microvascular perfusion, whereas DUS can only estimate flow within larger
vessels. This potential innovation for assessing the renal macro- and microvasculature may
allow for earlier non-invasive detection of DGF and acute rejection. With additional
research, it may ultimately be shown that non-invasive CEUS will revolutionize early DGF and
acute rejection diagnosis to enable improvement in long-term patient and allograft survival.
