Contact information
Type
Scientific
Primary contact
Prof William Rosenberg
ORCID ID
Contact details
Windeyer Institute of Medical Sciences
46 Cleveland Street
London
W1T 4JF
United Kingdom
+44 20 7794 0500
w.rosenburg@ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
RP-PG-0707-10101
Study information
Scientific title
Evaluating the benefits for patients and the UK National Health Service (NHS) of new and existing biological fluid markers in liver and renal disease: a prospective multicentre randomised trial
Acronym
ELUCIDATE
Study hypothesis
The primary aim of the study is to evaluate the benefits to patients and the NHS of new and existing biological fluid markers in liver and renal disease, which aims to develop a stringent approach to protein biomarker evaluation. This trial will determine whether the use of the enhanced liver fibrosis (ELF) test will significantly alter the diagnostic timing and subsequent management of cirrhosis of the liver in order to reduce serious complications and improve outcomes for patients and service provision.
Ethics approval
Not provided at time of registration
Study design
Prospective multicentre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Chronic liver disease
Intervention
Patients will be randomised to either:
1. ELF arm: patients in the ELF arm will undergo follow-up screening for cirrhosis with the ELF test
2. Standard care arm: patients in the standard care arm will undergo standard follow-up screening for cirrhosis
Patients will be followed up at 6 monthly intervals until 30 months after randomisation.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Time from clinical diagnosis of cirrhosis to incidence of any of the following severe complications:
1. Variceal haemorrhage
2. Mortality due to variceal haemorrhage
3. Spontaneous bacterial peritonitis
4. Mortality due to hepatocellular cancer (HCC)
Patients will undergo follow-up visits at 6-monthly intervals, increasing to 3-monthly intervals after diagnosis of cirrhosis, for 30 months post-randomisation. Outcome data will be collected at each visit.
Secondary outcome measures
1. Time from randomisation to clinical diagnosis of cirrhosis (to allow instigation of prophylaxis and screening)
2. Detection and timing of complications following cirrhosis, including:
2.1. Detection of small varices
2.2. Detection of large varices
2.3. Incidence of treatable hepatocellular cancer (HCC)
2.4. Incidence of inoperable HCC
3. All causes of mortality
4. Economic evaluation of the ELF test in the early detection of cirrhosis and as such in the initiation of measures to reduce the incidence of severe complications following cirrhosis
Patients will undergo follow-up visits at 6-monthly intervals, increasing to 3-monthly intervals after diagnosis of cirrhosis, for 30 months post-randomisation. Outcome data will be collected at each visit.
Overall trial start date
01/09/2009
Overall trial end date
01/09/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Registration:
1. Patients with chronic liver disease and pre-cirrhotic moderate to severe fibrosis as classified by clinical, laboratory, or histological evidence, due to viral hepatitis B or C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), haemochromatosis, or combinations of these diseases
2. Clinical evidence of chronic liver disease as evidenced by documented abnormalities of liver function for more than six months including:
2.1. Elevated liver enzymes (alanine aminotransferase [ALT], asparate aminotransferase [AST], gamma glutamyl-transferase [GGT])
2.2. Elevated bilirubin with raised liver enzymes
2.3. Symptoms or signs of chronic liver disease (including jaundice, clubbing, palmar erythema, spider naevae)
3. Chronic liver disease due to:
3.1. Virus-serological and nucleic acid evidence of chronic Hepatitis C, chronic Hepatitis B
3.2. Fat: ultrasound evidence of fatty liver disease
3.3. Alcohol: history of excessive alcohol consumption
3.4. Autoimmune hepatitis (smooth muscle antibodies [SMA], anti-nucleur antibodies [ANA], liver-kidney-microsome antibodies [LKMA] and raised immunoglobins)
3.5. Primary biliary cirrhosis (anti-mitochondrial antibodies [AMA], M2 antibodies)
3.6. Primary sclerosing cholangitis (endoscopic retrograde cholangiopancreatography [ERCP] or magnetic resonance cholangiopancreatography [MRCP] evidence of beading of biliary tree)
3.7. Haemochromatosis-HFE genotype HDCY or HHYY with liver biopsy evidence of iron overload
4. Aged greater than or equal to 18 years old and less than 75 years of age, either sex
5. Give their written, informed consent to participate
6. Likelihood of ability to comply with the follow-up schedule
7. Life expectancy greater than 6 months
Randomisation:
8. An ELF score of greater than or equal to 10.5
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1000
Total final enrolment
878
Participant exclusion criteria
Registration:
1. Unable to provide consent
2. Clinical, histological or laboratory diagnosis of cirrhosis (other than ELF) such as hepatic impairment as evidenced by any one of the following:
2.1. Platelets less than the lower limit of normal (LLN)
2.2. Albumin less than LLN
2.3. Ultrasound of other imaging evidence of cirrhosis (coarse echo texture, irregular outline to liver, splenomegally)
OR
3. Any episode of hepatic decompensation compatible with cirrhosis including:
3.1. Encephalopathy, variceal bleeding, ascites
3.2. Established diagnosis of hepatocellular cancer
3.3. Elevated alpha feto-protein without investigation to exclude HCC
4. Previously screened and found ineligible for the ELUCIDATE Trial
Note that human immunodeficiency virus (HIV) co-infection is NOT an exclusion criterion.
Randomisation:
5. An ELF score of less than 10.5
Recruitment start date
01/09/2009
Recruitment end date
01/09/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Windeyer Institute of Medical Sciences
London
W1T 4JF
United Kingdom
Sponsor information
Organisation
University of Leeds (UK)
Sponsor details
Woodhouse Lane
Leeds
LS2 9JT
United Kingdom
+44 (0)113 243 1751
governance-ethics@leeds.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) (UK) - Programme Grant for Applied Research (PGfAR) (ref: RP-PG-0707-10101)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2018 results in https://pubmed.ncbi.nlm.nih.gov/29995365/ (added 29/12/2020)