Enhanced Liver fibrosis (ELF) test to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Events

ISRCTN	ISRCTN74815110
DOI	https://doi.org/10.1186/ISRCTN74815110
Secondary identifying numbers	RP-PG-0707-10101

Submission date: 06/08/2009
Registration date: 11/11/2009
Last edited: 29/12/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof William Rosenberg
Scientific

Windeyer Institute of Medical Sciences
46 Cleveland Street
London
W1T 4JF
United Kingdom

Phone	+44 20 7794 0500
Email	w.rosenburg@ucl.ac.uk

Study information

Study design	Prospective multicentre randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	ELUCIDATE
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
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 study start date	01/09/2009
Completion date	01/09/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1000
Total final enrolment	878
Key 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
Key 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
Date of first enrolment	01/09/2009
Date of final enrolment	01/09/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Windeyer Institute of Medical Sciences

London
W1T 4JF
United Kingdom

Sponsor information

University of Leeds (UK)
University/education

Woodhouse Lane
Leeds
LS2 9JT
England
United Kingdom

Phone	+44 (0)113 243 1751
Email	governance-ethics@leeds.ac.uk
Website	http://www.leeds.ac.uk/
"ROR"	https://ror.org/024mrxd33

Funders

Funder type

Government

National Institute for Health Research (NIHR) (UK) - Programme Grant for Applied Research (PGfAR) (ref: RP-PG-0707-10101)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2018	29/12/2020	Yes	No

Editorial Notes

29/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
18/11/2016: No publications found in PubMed, verifying study status with principal investigator.