Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03165201 |
| Other study ID # |
PJM126 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 18, 2017 |
| Est. completion date |
October 1, 2020 |
Study information
| Verified date |
April 2021 |
| Source |
Perspectum |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This will be a prospective, multi-centre, biomarker trial comparing the accuracy of a new
test (LiverMultiScan) against an existing test (liver biopsy) in the assessment of liver
transplant recipients, designed in accordance with the STARD criteria.
Study participants are 200 patients with liver transplant, due to undergo liver biopsy as
part of serial evaluation of their liver health and to rule out rejection. The whole study
will take 3 years with 2 years of recruitment The main aim is to investigate whether the
introduction of LiverMultiScan as a standardised diagnostic test for liver disease can match
the diagnostic yield of existing biopsies.
Description:
Long-term survival after solid organ transplantation has increased during the last decade due
to improvements in surgical technique, peri-operative care, and more efficient
immunosuppression (IS) (1). However, transplant recipients still exhibit higher morbidity and
mortality than the general population. One of the main causes are co-morbidities which are
negatively influenced by chronic IS drug usage. It is however a very fine balance, as
under-usage of IS can lead to transplant rejection (2). Therefore, many paediatric and some
adult liver transplant recipients have regular liver biopsies as part of their serial
evaluation, so-called 'routine liver biopsies'. Biopsy is performed if there is suspected
rejection, as no current non-invasive tests are both sensitive and specific for rejection.
Biopsy is used to identify early histological signs of rejection. However, there are some
problems;
- There is a risk of complication due to biopsy(1 in 10,000)
- biopsies are painful
- sample only a tiny fraction of the liver and for children there is a need to sedate.
Therefore, they are less-than-perfect for serial evaluation. Optimisation of IS has become a
priority goal in transplantation, but is hampered by the lack of diagnostic tests available
for serial monitoring (3). There are potential benefits of IS minimization or withdrawal,
however this need to be balanced with the risks, inconveniences and costs of prompting liver
allograft rejection.
Identification of a reproducible and reliable non-invasive assessment tool for the
transplanted liver, such as multiparametric quantitative MRI, would therefore substantially
benefit the liver transplant population. In Europe, approximately 6000 liver transplants are
performed every year (1). Under the current standard-of-care, indefinite pharmacological IS
is prescribed to all of them. The cost of immunosuppressive drugs is €4200- €7000 per patient
per year (£3000-£5000/patient/year). In addition to its cost, chronic IS may result in
substantial side effects (hypertension, diabetes, renal insufficiency, hyperlipidaemia,
cancer, infections) that contribute to patient morbidity and mortality (2). Rejection is a
major concern with liver transplant recipients. At present, there is no clear non-invasive
diagnostic pathway to identify early rejection. We would like to see if the implementation of
LiverMultiScan (4) to monitor the transplant population and modify treatment can replace or
equal the yield of invasive liver biopsies in the post-transplant population.
Therefore, the aim of this study is to determine whether there is concordance between using
LiverMultiScan and liver biopsy in a post-liver transplant population.
The primary objective is to investigate whether the introduction of LiverMultiScan as a
standardised diagnostic test for liver disease can match the diagnostic yield of existing
biopsies.
The following are the secondary objectives;
- To determine patient feedback from this population (transplant recipients) on
LiverMultiScan.
- To assess how multiparametric MRI correlates with other measures of fibrosis and
rejection (eg elastography, blood tests) in the evaluation of these patients.
- To evaluate the utility of LMS in the diagnosis of de novo or recurrent liver disease
post transplant
- To evaluate biliary changes in post-transplant patients with quantitative MRCP
Patients who meet the inclusion criteria will be approached by a member of their clinical
care team and asked if they are interested in taking part in the study. Both adult and
paediatric patients with a liver transplant due to have a liver biopsy, being seen in
medical/gastroenterology clinic, will be invited to take part in the study.
Once a potential adult participant has expressed interest in the study, he/she will be
provided with a PIL (Patient Information Leaflet) and an opportunity to discuss his/her
eligibility and the details of the study with her family and doctor.
Age-appropriate written and verbal versions of the PIL and Informed Consent will be presented
to the paediatric participants and their guardians. Once the participants and/or their
guardians (as appropriate) have had time to consider the PIL (minimum 24 hr) and the
opportunity to discuss the study with their family, friends and GP, they will be contacted by
a member of the study team to check whether they would like to take part and to schedule a
study visit. At this point, the inclusion criteria will be explained to all potential female
participants of childbearing potential age, that they will not be able to take part in the
study if they are pregnant.
The informed consent process will be carried out during the first study visit.
Informed consent to have an extra MR scan in addition to usual care will be sought by an
appropriately trained member of the study team. Age-appropriate written and verbal versions
of the Participant Information and Informed Consent presented to the participants and their
guardians detailing no less than:
- The exact nature of the study;
- what it will involve for the participant;
- the implications and constraints of the protocol;
- and any risks involved in taking part.
It will be clearly stated that the participant is free to withdraw from the study at any time
for any reason without prejudice to future care, and with no obligation to give any reason
for withdrawal.
The participant will be allowed as much time as they wished to consider the information, and
the opportunity to ask questions from the Investigator, their GP or other independent parties
to decide whether they will participate in the study. Written Informed Consent will then be
obtained by means of participant-dated signature and dated signature of the person who
presented and obtained the Informed Consent. In the case of minors under 16 years of age,
consent will be taken from at least one guardian and assent from the child age 6 and above.
For adolescents aged 16-18, consent will be taken from the adolescents themselves. GPs will
also be informed about patient taking part in the study, with participants' consent.
