Condition category
Digestive System
Date applied
10/04/2019
Date assigned
11/07/2019
Last edited
15/07/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Alcoholic hepatitis is a form of alcohol-related liver disease characterised by liver failure in the context of recent and heavy alcohol consumption. Currently, liver biopsy is used to diagnose alcoholic hepatitis and remains difficult to predict the course of the disease and how to select the best treatment.
The purpose of this study is to investigate how we can reduce mortality in patients with alcoholic hepatitis. Samples and data collected from patients will be used to investigate whether a blood test can diagnose alcoholic hepatitis and so avoid the need for liver biopsy. It will also study tests to predict disease outcome, infection and kidney damage.

Who can participate?
Adults aged 18 years and over with clinical diagnosis of either Alcoholic Hepatitis (AH) or Acute Decompensation of Cirrhosis (AD).

What does the study involve?
After consent to take part the study involves a brief interview and medical examination to ensure eligibility. Blood (about 60ml - just over four tablespoons worth) and urine samples will be collected for infection screening, standard laboratory testing and study testing. In case of ascites (fluid that has accumulated in the abdomen) the study doctor will perform an ascitic tap (collection of this fluid). Tests will also be done for viral hepatitis infections and for HIV (AIDS) (unless already available). Pre-menopausal female will be tested for pregnancy. All of these tests are standard clinical care. If agreed, we will be using samples if liver biopsy is performed as standard clinical care. Each visit should take about one hour.
- AD patients will only be required to attend the initial screening – day 0 and baseline – day 1 assessments as these samples are comparison for a diagnostic test for AH.
- For patients with AH, the study will last for 90 days (3 months). AH patients will be seen for a study/research visit at 7, 14, 21, 28, and 90 days after standard of care treatment. The condition will be monitored and we will collect the data/samples at these time points while the patient is in the hospital. After discharge from hospital, the routine weekly assessments will cease and there will only be day 28 and day 90 assessments.
- The last visit at 90 days, AH patients will have further blood, urine, and stool samples taken.

What are the possible benefits and risks of participating?
The knowledge we gain from the study and looking at samples in the laboratory should help us improve the treatment offered to patients with alcohol-related liver disease in the future. There may be discomfort associated with the taking of blood samples via a needle. There may be the inconvenience of donating urine and stool samples.

Where is the study run from?
Imperial College London, UK

When is the study starting and how long is it expected to run for?
June 2019 to May 2022

Who is funding the study?
Medical Research Council

Who is the main contact?
Dr. Karolina Bogdanowicz, micah@imperial.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Karolina Bogdanowicz

ORCID ID

Contact details

Imperial Clinical Trials Unit
London
W12 7RH
United Kingdom
020 7594 0995
micah@imperial.ac.uk

Type

Scientific

Additional contact

Dr Karolina Bogdanowicz

ORCID ID

Contact details

Imperial Clinical Trials Unit
London
W12 7RH
United Kingdom
020 7594 0995
micah@imperial.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

19SM5048

Study information

Scientific title

Multicentre Cohort Study in Alcoholic Hepatitis

Acronym

MICAH

Study hypothesis

The aim of the study is to recruit patients with Alcoholic Hepatitis (AH), irrespective of severity, to evaluate performance of the prognostic scoring systems and diagnostic and prognostic biomarkers. In order to evaluate diagnostic biomarkers, we will also recruit control patients with acute decompensation of cirrhosis (AD).

Ethics approval

Not provided at time of registration

Study design

Prospective multi-centre cohort study

Primary study design

Observational

Secondary study design

Nested case-control study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Alcoholic Hepatitis
Acute Decompensation of Cirrhosis (control group)

Intervention

Patients will continue to receive standard of care treatment throughout. Study participants will attend several test sessions where routine samples and other data will be collected.

After consent to take part the study involves a brief interview and medical examination to ensure eligibility. Blood and urine samples will be collected for infection screening, standard laboratory testing and study testing. In case of ascites, the study doctor will perform an ascitic tap. Tests will also be done for viral hepatitis infections and for HIV (AIDS) (unless already available). Pre-menopausal female will be tested for pregnancy. All of these tests are standard clinical care. If agreed, we will be using samples if liver biopsy is performed as standard clinical care. Each visit should take about 1 hour.
- AD patients will only be required to attend the initial screening – day 0 and baseline – day 1 assessments as these samples are comparison for a diagnostic test for AH.
- For patients with AH, the study will last for 90 days (3 months). AH patients will be seen for a study/research visit at 7, 14, 21, 28, and 90 days after standard of care treatment. The condition will be monitored and we will collect the data/samples at these time points while the patient is in the hospital. After discharge from hospital, the routine weekly assessments will cease and there will only be day 28 and day 90 assessments.
- The last visit at 90 days, AH patients will have further blood, urine, and stool samples taken.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Validation of diagnostic and prognostic performance parameters for (Baseline, D28, D90):
1. Taurocholic acid diagnostic test to distinguish AH from AD
2. Transferrin, ELF and PNPLA3 genotype adjusted prognostic scores
3. Bacterial DNA, monocyte HLADR expression and oxidative burst for prediction of infection
4. Bacterial DNA for risk stratification before immunosuppressive therapy
5. Micro RNAs for prediction of AKI
6. BLISS assay for prediction of response to prednisolone

Secondary outcome measures

1. Outcome at 28 and 90 days:
1.1 Mortality (rate)
1.2 Incidence of infection (rate)
1.3 Incidence of AKI (rate)
1.4 Incidence of recidivism (rate)
2. Outcome at 1, 5 and 10 years:
2.1 All-cause mortality (rate)
2.2 Liver-related mortality (rate)
2.3 Use of healthcare services (HES data)

Overall trial start date

01/03/2019

Overall trial end date

31/05/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Alcoholic Hepatitis group:
1.1 Aged 18 years or older
1.2 Clinical diagnosis of alcoholic hepatitis:
1.2.1 Serum bilirubin ≥ 50μmol/L
1.2.2 History of excess alcohol (> 80g/day male, > 60g/day female) to within 2 months of recruitment
1.3 Less than 4 weeks since admission to hospital
1.4 Informed consent
The alcoholic hepatitis cohort will be subdivided into patients with Maddrey’s discriminant function ≥32, referred to as severe alcoholic hepatitis (SAH) and those with Maddrey’s discriminant function <32, referred to as non-severe alcoholic hepatitis (NSAH).

2. Acute Decompensation of Cirrhosis group:
2.1 Aged 18 years or older
2.2 Clinical or radiological diagnosis of liver cirrhosis
2.3 Acute development of one or more of the following complications:
2.3.1 Ascites
2.3.2 Encephalopathy
2.3.3 Gastrointestinal haemorrhage
2.3.4 Infection
2.4 Less than 4 weeks since admission to hospital
2.5 Informed consent
2.6 History of excess alcohol (> 80g/day male, > 60g/day female) for more than 5 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1,000

Participant exclusion criteria

1. Acute Decompensation of Cirrhosis group:
1.1 Abstinence of >2 months prior to randomisation
1.2 Duration of clinically apparent jaundice > 3 months
1.3 Other causes of liver disease including:
1.3.1 Evidence of active chronic viral hepatitis (Hepatitis B or C)
1.3.2 Biliary obstruction
1.3.3 Hepatocellular carcinoma
1.4 Evidence of current malignancy (except non-melanotic skin cancer)
1.5 HIV infection
1.6 Aspartate Aminotransferase (AST) >500 U/L or Alanine Aminotransferase (ALT) >300 U/L (not compatible with alcoholic hepatitis)
1.7 Patients with a serum creatinine >500 μmol/L or requiring renal support (see below)
1.8 Patients dependent upon inotropic support (adrenaline or noradrenaline). Terlipressin is allowed
1.9 Active gastrointestinal bleeding
1.10 Untreated infection
1.11 Pregnant or lactating women
1.12 Patients who cannot understand English

2. Acute Decompensation of Cirrhosis group:
2.1 Alcoholic Hepatitis (clinically or on histology)
2.2 Other causes of liver disease including:
2.2.1 Evidence of active chronic viral hepatitis (Hepatitis B or C)
2.2.2 Biliary obstruction
2.2.3 Hepatocellular carcinoma
2.3 Pregnant or lactating women
2.4 HIV infection
2.5 Patients who cannot understand English

Recruitment start date

01/06/2019

Recruitment end date

31/05/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College Healthcare NHS Foundation Trust
St Marys Hospital Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

Plymouth Hospitals NHS Trust
Derriford Hospital
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

University Hospital Southampton NHS Foundation Trust
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital
Southampton
S5 7AU
United Kingdom

Trial participating centre

Royal Devon and Exeter NHS Foundation Trust
Royal Devon and Exeter Hospital
Exeter
Ex2 5DW
United Kingdom

Trial participating centre

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrookies Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Nottinghamshire Healthcare NHS Foundation Trust
The Resource, Trust HQ
Nottingham
NG3 6AA
United Kingdom

Trial participating centre

Royal Free London NHS Foundation trust
Royal Free Hospital
London
NW3 2QG
United Kingdom

Trial participating centre

The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital
Newcastle
NE7 7DN
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Marlborough Street; Bristol Avon
Bristol
BS1 3NU
United Kingdom

Trial participating centre

Derby Teaching Hospitals NHS Foundation Trust
Royal Derby Hospital
Derby
DE22 3NE
United Kingdom

Trial participating centre

NHS Greater Glasgow and Clyde
Glasgow Royal Infirmary; Queen Elizabeth University Hospital
Glasgow
G12 0XH
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Aintree University Hospital NHS Foundation Trust
University Hospital AIntree
Liverpool
L9 7AL
United Kingdom

Trial participating centre

Blackpool Teaching Hospitals NHS Foundation trust
Victoria Hospital
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

Chelsea and Westminster Hospital NHS Foundation trust
Chelsea and Westminster Hospital
London
SW10 9NH
United Kingdom

Trial participating centre

Torbay and South Devon NHS Foundation Trust
Hengrave House, Torbay Hospital
Devon
TQ2 7AA
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Kings College Hospital NHS Foundation Trust
Kings College Hospital
London
SE5 9RS
United Kingdom

Trial participating centre

Gloucestershire Hospitals NHS Foundation Trust
Alexandra House
Cheltenham
GL53 7AN
United Kingdom

Trial participating centre

Royal Cornwall Hospitals NHS Trust
Royal Cornwall Hospital
Cornwall
TR1 3LJ
United Kingdom

Trial participating centre

The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Royal Bournemouth General Hospital
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

Hull and East Yorkshire Hospitals NHS Trust
Hull Royal Infirmary
Hull
Hu3 2JZ
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
Bradford Royal Infirmary
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust
Doncaster Royal Infirmary
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

ST Georges University Hospitals NHS Foundation Trust
St Georges Hospital
London
SW17 0QT
United Kingdom

Trial participating centre

Portsmouth Hospitals NHS Trust
Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Poole Hospital NHS Foundation Trust
Poole Hospital
Poole
BH15 2JB
United Kingdom

Trial participating centre

Luton and Dunstable University Hospital NHS Foundation Trust
Luton and Dunstable University Hospital
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Chesterfield Royal Hospital NHS Foundation Trust
Chesterfield Royal Hospital
Chesterfield
S44 5BL
United Kingdom

Trial participating centre

County Durham and Barlington NHS Foundation Trust
Darlington Hospital
Durham
DL3 6HX
United Kingdom

Trial participating centre

NHS Tayside
Kings Croos
Dundee
DD3 8EA
United Kingdom

Trial participating centre

Abertawe Bro Morgannwg University LHB
One Talbot Gateway
West Glamoran
SA12 7BR
United Kingdom

Trial participating centre

South Tyneside NHS Foundation Trust
South Tyneside District Hospital
Southshields Tyne and Wear
Ne34 0PL
United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Medical Centre
West Midlands
B15 2TH
United Kingdom

Trial participating centre

City Hospitals Sunderland NHS Foundation Trust
Sunderland Royal Hospital
Sunderland Tyne and Wear
SR4 7TP
United Kingdom

Trial participating centre

Countess of Chester Hospital NHS Foundation Trust
Countess of Chester Hospita
Chester
CH2 1UL
United Kingdom

Trial participating centre

University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Northumbria Healthcare NHS Foundation Trust
Rake Lane
North Shields Tyne and wear
NW29 8NH
United Kingdom

Trial participating centre

NHS Lothian
Waverley Gate
Edingburgh
EH1 3EG
United Kingdom

Trial participating centre

South Tees Hospitals NHS Foundation Trust
James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Taunton and Somerset NHS Foundation Trust
Musgrove Park Hospital
Taunton Somerset
TA1 5DA
United Kingdom

Trial participating centre

Firmley Health NHS Foundation Trust
Portsmouth Road
Surrey
GU16 7UJ
United Kingdom

Trial participating centre

Sandwell and West Birmingham Hospitals NHS Trust
City Hospital
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Sherwood Forest Hospitals NHS Foundation Trust
Mansfield Road
Sutton In Ashfield
NG17 4JL
United Kingdom

Trial participating centre

North Staffordshire Combined Healthcare NHS Trust
Bellringer Road
Stoke on Trent
St4 8HH
United Kingdom

Trial participating centre

Warrington and Halton Hospitals NHS Foundation Trust
Warrington Hospital
Cheshire
Wa5 1qg
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

NHS Forth Valley
33 Spittal Street
Stirling
FK8 1DX
United Kingdom

Trial participating centre

Western Sussex Hospitals NHS Foundation Trust
Worthing Hospital
Worthing
BN11 2DH
United Kingdom

Trial participating centre

NHS Grampian
Summerfield House
Aberdeen
AB15 6RE
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

Medical School Building
St Marys Campus
Norfolk Place
London
W2 1PG
United Kingdom
020 7589 5111
jrco@ic.ac.uk

Sponsor type

University/education

Website

http://www.imperial.ac.uk/

Funders

Funder type

Government

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The results of the MICAH study may take approximately 1 year to be reported. The results will be published in a medical journal and presented at appropriate clinical conferences.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository.

No identifiable personal data will be included in any publications resulting from research. Data generated by the study will be held on the InForm eCRF online database. The database will not be used to store any raw data. NHS identifiable patient data will only be stored on secure computers which may only be accessed by the clinicians involved in the patients' clinical care. Paper records (consent forms etc) will be stored securely on NHS premises. Information gleaned from access will remain entirely confidential, and will only be recorded anonymously in study. Under the General Data Protection Regulation (GDPR) the study database will assign a unique identifying numerical code which is distinct from the NHS number of the hospital record number. The unique identifier will be used for all NHS or Imperial College research data stored on investigators computers accessible only to members of the research/healthcare team. This pseudoanonymised data will be kept on NHS and University computers. Such data will be encrypted to the local ICT requirements. Only fully anonymised data will be kept on University computers and laptops.

Intention to publish date

09/09/2022

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

15/07/2019: Internal review. 15/04/2019: Trial’s existence confirmed by the Medical Research Council