Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03709030 |
| Other study ID # |
13946 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 17, 2019 |
| Est. completion date |
December 31, 2020 |
Study information
| Verified date |
May 2021 |
| Source |
Perspectum |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This pilot study aims to determine the utility of direct Magnetic Resonance
Cholangiopancreatography (MRCP) in the assessment of suspected acute gallstone disease
presentations. This will take the form of a randomized controlled trial, the design of which
is based on recent internal audit data which indicated that a high proportion of patients
ultimately require MRCP prior to diagnosis, treatment and discharge, and suggested that early
scan may improve overall costs and outcomes. Patients with symptoms and signs suggestive of
suspected gallstone disease and deranged liver function tests/amylase (i.e. suggestive of a
potentially obstructive gallstone disease), will be enrolled across the full range of
'front-door' locations for surgical presentations within the hospital (Emergency Department,
Surgical Emergency Unit, Ambulatory Assessment Unit), and randomized to one of two diagnostic
pathways which are both existing variations in current clinical care:
1. MRCP is used as the first mode of imaging;
2. following a standard care model (ultrasound then MRCP if deemed appropriate). An
assessment will then be undertaken of the cost-effectiveness of early MRCP versus
standard care, using the primary outcome measure of cost to diagnostic scan report
calculated using hospital episode statistics (HES), with secondary outcome measures to
assess the overall utility which include length of stay, time to diagnosis, overall cost
of admission using HES, in-hospital complications, Patient Reported Outcome Measures
(PROMs), readmission and re-attendance rates (ED/GP), and service/radiology costs.
Description:
Acute biliary disease comprises a significant proportion of surgical presentations in
Accident and Emergency departments (A&E), as well as of emergency surgical admissions to
secondary care. Historically, this patient group first undergoes an abdominal ultrasound to
confirm the presence of gallstones and look at ancillary features that may suggest
cholecystitis or the presence of bile duct stones. The vast majority of patients who have
abnormal liver biochemistry then proceed to Magnetic resonance cholangiopancreatography
(MRCP), because the ultrasound scan is unable to clarify matters sufficiently to satisfy
clinical need. There is often considerable delay in carrying out two sequential imaging
investigations for each patient.
A number of studies have raised questions regarding the utility of ultrasound in acute
biliary disease. The prevalence of Common Bile Duct (CBD) stones in patients with
cholelithiasis is significant at 5-15%. CBD diameter, often used in US reporting as a marker
of the presence of choledocholithiasis, may not correspond to the presence of a CBD stone -
in one study, only 37% of patients with CBD stones had CBD dilatation on ultrasound.
Ultrasound is a user-dependent technology, where the seniority of the scanner can influence
the reliability of the report, and a 2013 study by Barlow et al. suggested that ultrasound
findings in the context of deranged LFTs are often inaccurate in predicting CBD stones in
gallstone pancreatitis, suggesting that MRCP be used to improve diagnosis. A 2015
retrospective study led by Qiu et al. found the sensitivity of peri-operative ultrasound for
CBD stones to be very low at 44.95% and supported the use of MRCP as a diagnostic test if CBD
stones were suspected. They also suggested the potential for economic benefits of using MRCP
over US in patients with potential choledocholithiasis.
MRCP has been shown to be more cost-effective than US in selecting patients for Endoscopic
Retrograde Cholangio-Pancreatography (ERCP) with suspected CBD stones, has a comparable
accuracy to ERCP 6, and has been shown to reduce the number of unnecessary ERCPs performed in
gallstone patients 7. Epelboym (2013) and Nebiker (2009) however disagree, characterising the
use of MRCP in such patients as expensive and inefficient, and support the use of ultrasound
as the primary diagnostic modality 8,9.
In a recent paper, Milburn et al conducted a retrospective study examining the patient
journeys corresponding to 234 inpatient MRCP scans over a 2-year period. They found that
increasing access to MRCP led to further interventions in 22% of cases due to an increased
detection of complications and alternate pathologies (e.g. malignancy), and therefore
increased overall length of stay. The median duration from request to scan was 2 days, with a
further 1 day to scan report (therefore 3 days overall from request to report). They
suggested improved access and timely reporting of MRCP could potentially reduce length of
stay, though it may also increase the number of interventions 10. Clearly, there is a need to
examine whether proceeding directly with MRCP (without preceding ultrasound) would prove to
be cost-effective for these patients, and with a growing body of evidence as to the utility
of early diagnosis to hasten the patient journey and improve treatment outcomes, further
research is needed to determine whether the use of direct MRCP may be beneficial in this
regard.
A recent audit of patients seen in the John Radcliffe Hospital ED over a period of six weeks
revealed 46 patients admitted with gallstone disease, an incidence of approximately 1
admission per day. This correlates well with local audit of surgical admissions, which gives
a referral rate of approximately 2 patients a day with 45% of patients referred from ED and
55% being referred from primary care. Despite the broad range of pathologies encountered in
the ED and the considerable overlap in presentation, the diagnostic accuracy of emergency
physicians with respect to gallstone disease was high, with the suggested specificity of an
ED cholecystitis diagnosis calculated at around 85%, based largely on clinical findings and
blood tests without radiological confirmation. This suggests that ED clinicians may be able
to identify patients whose presenting symptoms are likely to be secondary to acute gallstone
disease with a reasonable degree of accuracy on a clinical basis alone. Subsequent analysis
of the continued inpatient diagnostic pathways suggested that whilst ultrasound remains the
initial diagnostic radiological modality in the majority of patients with such presentations,
approximately 59% (27/46) of patients undergo cross-sectional imaging during their admission,
with around 48% (22/46) undergoing inpatient MRCP. Whilst access times to MRCP have improved
in recent years, this pathway nevertheless may potentially result in an unnecessarily
extended time to definitive diagnosis, and potentially unnecessary radiological expenditure.
This raises the possibility that using MRCP as the initial diagnostic test in such patients
may improve pathway efficiency, reduce length of stay and radiological burden, and hence
reduce admission costs, notwithstanding the potential for improved diagnostic accuracy and
detection of pathology such as common bile duct stones and/or pancreatitis. It may also
improve patient satisfaction and clinical outcomes (e.g. earlier access to ERCP and stone
removal in biliary obstruction patients). This can be assessed in a prospective randomised
study to assess utility.
This pilot study aims to determine the utility of direct Magnetic Resonance
Cholangiopancreatography (MRCP) in the assessment of suspected acute gallstone disease
presentations. This will take the form of a randomized controlled trial, the design of which
is based on recent internal audit data which indicated that a high proportion of patients
ultimately require MRCP prior to diagnosis, treatment and discharge, and suggested that early
scan may improve overall costs and outcomes. Patients with symptoms and signs suggestive of
suspected gallstone disease and deranged liver function tests/amylase (i.e. suggestive of a
potentially obstructive gallstone disease), will be enrolled across the full range of
'front-door' locations for surgical presentations within the hospital (Emergency Department,
Surgical Emergency Unit, Ambulatory Assessment Unit), and randomized to one of two diagnostic
pathways which are both existing variations in current clinical care:
1. MRCP is used as the first mode of imaging;
2. following a standard care model (ultrasound then MRCP if deemed appropriate). An
assessment will then be undertaken of the cost-effectiveness of early MRCP versus
standard care, using the primary outcome measure of cost to diagnostic scan report
calculated using hospital episode statistics (HES), with secondary outcome measures to
assess the overall utility which include length of stay, time to diagnosis, overall cost
of admission using HES, in-hospital complications, Patient Reported Outcome Measures
(PROMs), readmission and re-attendance rates, and service/radiology costs.
In addition to standard MRCP scan processing by the radiology department, data obtained
through this study will be processed using the new quantitative MRCP+ technology (provided by
Perspectum Diagnostics) to assess its diagnostic efficacy in detecting biliary tree
dilatation, stones or strictures. Perspectum Diagnostics' quantitative MRCP technology is a
software package which allows previously acquired MRCP data to be enhanced and quantitatively
characterised using advanced image processing techniques (MRCP+). Conventional MRCP scans can
be difficult to interpret since the 2D representation suffers from occlusion problems and a
lack of depth information. This new technology can enhance the data without the need for
contrast agent, enabling the visualization of smaller ducts. Quantitative characterisation of
the biliary tree computes biliary tube diameter at each point along the duct, along with
information about the cross-section orientation and branching topology. Combining true 3D
rendering of the enhanced data with quantitative characterization facilitates clear mapping
of the biliary tree, which can potentially improve surgical planning, facilitate detection of
strictures, dilatations and gallstones in suspected biliary colic presentations and
objectively stratify patients. As yet however this application of the MRCP+ has not been
fully assessed in clinical practice, and this subsequent part of the study would aim to
address this and provide data to enable assessment of its diagnostic utility.
