Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03376009 |
| Other study ID # |
AC1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 15, 2018 |
| Est. completion date |
September 10, 2018 |
Study information
| Verified date |
May 2024 |
| Source |
University of Edinburgh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Kidney dysfunction before and immediately after liver transplantation is common and leads to
poorer outcomes, including prolonged need for post-operative intensive care, diminished graft
survival, and greater risk of permanent kidney dysfunction and death. Blood creatinine level
- the standard measure of kidney function - is suboptimal in people with advanced liver
disease, overestimating kidney function by >20%. There is significant concern that liver
transplant recipients are at higher risk of acute kidney injury (AKI) than we can currently
predict. This study aims to identify superior tests (blood/urine or imaging) for kidney
dysfunction, to enable improved treatment and patient outcomes.
This study aims to recruit 80-100 consecutive patients admitted to the Scottish Liver
Transplant Unit (SLTU), Royal Infirmary of Edinburgh (RIE) for liver transplant assessment
over a 6 month period. Permission will be sought to record the results of routine tests
performed by the NHS during this assessment week. These tests include: electrocardiograph
(ECG), Computed Tomography (CT) liver and abdomen, cardio-pulmonary exercise testing (CPEX),
pulmonary function tests (PFTS), routine haematology and biochemistry blood tests, 24 hour
urine collection and body composition analysis.
In addition, we will invite participants to attend the RIE clinical research facility (CRF)
for a single visit (~2 hours) to perform extra research assessments. Blood and urine will be
collected for biomarker analysis. Non-invasive assessment of cardiovascular function will be
completed using cardiac bio-impedance and aortic pulse wave velocity. Examination of the
blood vessels at the back of the eye will be performed using optical coherence tomography.
A subgroup of 10 participants will undergo magnetic resonance imaging (MRI) of the kidneys
using arterial spin labelling to identify dysregulated renal perfusion. Patients who are
transplanted during the study timeframe will be asked to re-attend the CRF for repeat
assessments at 6 weeks post transplantation.
Funded by Scottish Liver Transplant Unit Endowment Fund
Description:
Study population:
This prospective observational study will aim to recruit 80-100 consecutive patients admitted
for liver transplant assessment to the Scottish Liver Transplant Unit in the Royal Infirmary
of Edinburgh over a 6 month period.
Consent:
Potential participants will be identified by the clinical team involved in the patient's
care. Thereafter, potentially suitable participants will be given information about the study
both verbally (by a member of the research team) and in writing in the form of the patient
information sheet. Potential patients will be given time (up to 24 hours) to consider their
participation and discuss this with friends or family. If participants remain interested,
written consent will be taken by the principal investigator or a suitably qualified and
delegated member of the study site staff.
Study overview:
If the study entry criteria are met, and written consent is obtained the participant will be
recruited to the study. Thereafter, permission will be sought to record the routine NHS
administrative data (clinical, radiological and laboratory blood tests) that is collected as
part of the routine NHS transplant assessment visit.
At a suitable time during the week long transplant assessment admission the participant will
be transferred to theClinical Research Facility on the ground floor of the RIE for a 1-2 hour
visit. During this study visit the following tests will be performed:
1. Blood tests:
•Serum/plasma biomarkers: Approximately 10ml (3 teaspoons) of blood will be extracted to
measure pre-specified biomarkers of renal injury including kidney injury molecule-1
(KIM-1), cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Samples will
then be stored to facilitate measurement of additional biomarkers in the future. This
point will be clear in the patient information sheet and consent form.
2. Urine tests:
•Urinary biomarkers: A random urine sample will be obtained to measure urinary protein
to creatinine ratio (uPCR), KIM-1 and liver-type fatty acid binding protein (L-FABP)
3. Imaging/monitors:
- Cardiac bio-impedance - a non-invasive assessment of cardiac output, cardiac index
and systemic vascular resistance index using the bio-impedence technique
(Cardioscreen 1000 Medis) Cardiac bio-impedance is performed by attaching sticky
electrodes to the participant's neck and thorax. These electrodes pass a very low,
constant and alternating current (1.5 mA, 86 kHz) across the thorax, which is
imperceptible to the patient. This provides beat by beat data on cardiac output and
haemodynamic measurements.
- Aortic pulse wave velocity (APWV) - a non-invasive measure of arterial function
using oscillometric recordings at the brachial artery detailing both peripheral and
central haemodynamics. This will be measured using two different technique
(TensioMed Arteriograph and SphygmoCor)
TensioMed Arteriograph: Aortic pulse wave velocity is performed by applying a blood
pressure cuff to the participant's upper arm. After a rest period the test is started
and the blood pressure cuff inflates and deflates twice. This process takes
approximately three minutes and should cause only mild, temporary discomfort. The test
will routinely be performed in duplicate to ensure accuracy of results.
SphygmoCor: A pressure sensor is initially held over the radial pulse at the wrist to
analyse the pulse wave. This sensor is then held over the carotid artery (side of the
neck) and femoral artery (top of the leg) to assess the speed of the pulse wave through
the body (pulse wave velocity). The probe is similar to an ultrasound probe and should
not cause any discomfort to the patient.
•Optical Coherence Tomography (OCT) (Spectralis OCT) -is a non-invasive imaging test
which uses light waves to take cross sectional images of the back of the eye.
Examination of the retinal and retinal nerve fibre layer thickness, macular volume, and
choroidal thickness provides an assessment of generalised systemic microvascular injury.
A strong correlation between choroidal thickness and renal dysfunction has previously
been shown in patients with chronic kidney disease (Balmforth C et al, JCI Insight
2016).
The participant is asked to sit in front of the OCT machine and rest their chin on a
support to keep it motionless. The equipment will then scan the eye without touching it.
Scanning takes about 5 - 10 minutes.
In a subgroup of 10 patients:
•Magnetic resonance imaging using arterial spin labelling (ASL-MRI) This promising
quantitative technique has the potential to identify dysregulated renal perfusion and
stratify risk of AKI in pre-OLT patients, and to monitor alterations in renal
haemodynamics in the post transplantation setting.
- We aim to recruit 5 participants with 'normal' renal function
(eGFR≥60ml/min/1.73m2) and a further 5 participants with 'abnormal' renal function
(eGFR<60ml/min/1.73m2)
- In order to reduce the risk of selection bias we will approach consecutive patients
to invite them to join this subgroup.
- Weekly recruitment may be limited by scanner availability.
- ASL-MRI will be performed in this subgroup during the week of OLT assessment and
then repeated at 6-weeks post transplantation in those participants who undergo OLT
during the study period.
- Participants will be excluded if they have contra-indications to MRI.
This test requires the participant to lie flat in the scanner for approximately 30
minutes. The participant will be able to talk to the professional performing the scan at
all times, but they will not be allowed to move around whilst the scan is being
performed. The participant will be asked to hold their breath for short periods of time
(15-20 seconds) throughout the scan to allow image acquisition. Full details of this
procedure will be given to the participant in the information leaflet. Those who are
claustrophobic, who have an implantable device such as a pacemaker, and those who will
find it prohibitively uncomfortable to lie in the scanner for approximately 30 minutes
will be excluded from this subgroup.
Participants who are transplanted during the timeframe of the study will be asked to
attend the RIE CRF for a 1-2 hour follow-up visit at approximately 6-weeks
post-transplantation (to coincide with their routine transplant clinic appointment).
The following tests will be repeated:
- Routine haematology and biochemistry tests
- Biomarkers - urine/serum/plasma including uPCR
- Cardiac bio-impedence
- APWV
- OCT
- ASL-MRI - only if performed pre-transplant
Morbidity data will be collected for all patients including need for renal replacement
therapy (RRT) and change in renal function over time (ΔeGFR; change in estimated
glomerular filtration rate).
For those patients who receive a liver transplant during the 6 month study period;
length of hospital stay, length of ITU admission, warm ischaemic time (time spent
transplanting organ) and graft function will also be recorded.
Mortality data will be obtained from Trak and transplant unit source data. Permission
will be sought to obtain mortality data until 1-year post transplantation.
