Multicentre Cohort Study in Alcoholic Hepatitis
| ISRCTN | ISRCTN24883155 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN24883155 |
| Secondary identifying numbers | 19SM5048 |
- Submission date
- 10/04/2019
- Registration date
- 11/07/2019
- Last edited
- 16/02/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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 December 2023
Who is funding the study?
Medical Research Council
Who is the main contact?
Dr. Karolina Bogdanowicz, micah@imperial.ac.uk
Contact information
Public
Imperial Clinical Trials Unit
London
W12 7RH
United Kingdom
| Phone | 020 7594 0995 |
|---|---|
| micah@imperial.ac.uk |
Scientific
Imperial Clinical Trials Unit
London
W12 7RH
United Kingdom
| Phone | 020 7594 0995 |
|---|---|
| micah@imperial.ac.uk |
Study information
| Study design | Prospective multi-centre cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Nested case-control study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Multicentre Cohort Study in Alcoholic Hepatitis |
| Study 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(s) | Not provided at time of registration |
| Condition | Alcoholic hepatitis or 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 |
| 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 study start date | 01/03/2019 |
| Overall study end date | 31/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1,000 |
| 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 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 | 31/05/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Praed Street
London
W2 1NY
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Southampton
SO16 6YD
United Kingdom
Southampton
S5 7AU
United Kingdom
Exeter
Ex2 5DW
United Kingdom
Liverpool
L7 8XP
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Nottingham
NG3 6AA
United Kingdom
London
NW3 2QG
United Kingdom
Newcastle
NE7 7DN
United Kingdom
Bristol
BS1 3NU
United Kingdom
Derby
DE22 3NE
United Kingdom
Glasgow
G12 0XH
United Kingdom
Oxford
OX3 9DU
United Kingdom
Liverpool
L9 7AL
United Kingdom
Blackpool
FY3 8NR
United Kingdom
London
SW10 9NH
United Kingdom
Devon
TQ2 7AA
United Kingdom
Nottingham
NG7 2UH
United Kingdom
London
SE5 9RS
United Kingdom
Cheltenham
GL53 7AN
United Kingdom
Cornwall
TR1 3LJ
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Hull
Hu3 2JZ
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Doncaster
DN2 5LT
United Kingdom
London
SW17 0QT
United Kingdom
Portsmouth
PO6 3LY
United Kingdom
Poole
BH15 2JB
United Kingdom
Luton
LU4 0DZ
United Kingdom
Chesterfield
S44 5BL
United Kingdom
Durham
DL3 6HX
United Kingdom
Dundee
DD3 8EA
United Kingdom
West Glamoran
SA12 7BR
United Kingdom
Southshields Tyne and Wear
Ne34 0PL
United Kingdom
West Midlands
B15 2TH
United Kingdom
Sunderland Tyne and Wear
SR4 7TP
United Kingdom
Chester
CH2 1UL
United Kingdom
Leicester
LE1 5WW
United Kingdom
North Shields Tyne and wear
NW29 8NH
United Kingdom
Edingburgh
EH1 3EG
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Taunton Somerset
TA1 5DA
United Kingdom
Surrey
GU16 7UJ
United Kingdom
Birmingham
B18 7QH
United Kingdom
Sutton In Ashfield
NG17 4JL
United Kingdom
Stoke on Trent
St4 8HH
United Kingdom
Cheshire
Wa5 1qg
United Kingdom
Leeds
LS9 7TF
United Kingdom
Stirling
FK8 1DX
United Kingdom
Worthing
BN11 2DH
United Kingdom
Aberdeen
AB15 6RE
United Kingdom
Sponsor information
University/education
Medical School Building
St Marys Campus
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | 020 7589 5111 |
|---|---|
| jrco@ic.ac.uk | |
| Website | http://www.imperial.ac.uk/ |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| 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 plan | 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. |
Editorial Notes
16/02/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/11/2022 to 31/05/2023.
2. The overall trial end date was changed from 28/02/2023 to 31/12/2023.
3. The intention to publish date was changed from 30/05/2023 to 31/12/2023.
17/05/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/05/2022 to 30/11/2022.
2. The intention to publish date has been changed from 09/09/2022 to 30/05/2023.
11/03/2022: The overall trial end date has been changed from 31/05/2022 to 28/02/2023 and the plain English summary has been updated accordingly.
13/03/2020: Internal review.
15/07/2019: Internal review.
15/04/2019: Trial’s existence confirmed by the Medical Research Council
