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Trial registered on ANZCTR


Registration number
ACTRN12619000710123p
Ethics application status
Submitted, not yet approved
Date submitted
11/04/2019
Date registered
13/05/2019
Date last updated
13/05/2019
Date data sharing statement initially provided
13/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
When drugs don't work: A psychological intervention for Alcohol Related Liver Disease.
Scientific title
Psychological Treatment for Alcohol Related Liver Disease: Assessing Patient Engagement, Retention, and Drinking Behaviour.
Secondary ID [1] 298119 0
None
Universal Trial Number (UTN)
U1111-1230-4489
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alcoholic Hepatitis 312116 0
Alcohol Related Liver Disease 312117 0
Alcohol Use Disorder 312118 0
Condition category
Condition code
Oral and Gastrointestinal 310672 310672 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Mental Health 310673 310673 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are referred to this outpatient alcohol and drug service following inpatient hospital admission, by their General Practitioner, or self-referral. Initial assessment is conducted by a clinical nurse or social worker. Initial assessment includes standardised review of psychosocial history, dependency symptoms, dependence severity, and comorbid drug use. Suitable patients are enrolled in the Cognitive-Behavioural Therapy (CBT) for Alcohol Use Disorder (AUD) program. When enrolled in the program patients receive a 1-hour consult with an addiction specialist physician, comprising a medical review, physical examination, assessment of suitability for prescription of adjunct pharmacotherapy (e.g. Acamprosate or naltrexone), and a written report to their primary health-care provider with recommendations for ongoing management. The CBT for AUD program comprises 8x 1hour face-to-face outpatient sessions over 3 months with a clinical psychologist. Following three months of abstinence, less frequent contact is maintained. Breathalyser readings are mandatory and routinely undertaken prior to each session. Standardised assessments are administered each session, monitoring: drinking behaviours (quantity, frequency), adherence to adjunct pharmacotherapy, alcohol craving, and alcohol refusal self-efficacy. The first session is devoted to obtaining a thorough assessment of the problem (including a comprehensive psychometric battery), education about the potential harms associated with alcohol, and affirming commitment to alcohol abstinence for the duration of the program. A CBT intervention plan is then developed collaboratively based on individual needs. The most common targets for intervention include: identification and alteration of alcohol expectancies, enhancement of drinking refusal self-efficacy, craving management, development of alternative coping strategies, problem-solving skills training, goal setting, and lifestyle improvement.

The Tailored Alcoholic Hepatitis (AH) Intervention will match for the existing generic face-to-face CBT Intervention historical benchmark for length of treatment (3 months) and therapist contact (8 hours). When possible, AH patients will be assessed as inpatients, including 1x addiction specialist physician assessment and 1x clinical psychologist review. The clinical psychologist will outline the services available to the patient, offering the CBT for AUD program as a means of ongoing support as an outpatient. Hospital discharge is determined by the treating medical team, not this service.

Post-inpatient hospital discharge, patients will either enrol in The CBT for AUD program or receive 2 x weekly 20 min ‘booster’ telephone sessions for 3 months (totalling 8 hours). The mode of treatment delivery (face-to-face or telephone) will be determined by geographical feasibility. Face-to-face sessions are preferred. Psychometric assessment and intervention targets will not be affected by modality, though AH patients are likely to require greater emphasis on health and lifestyle factors associated with adherence to treatment for AH. Treatment adherence is determined by session attendance, psychometric assessment at each session, and patient self-report of drinking behaviour.

This study is a non-randomised trial. All patients will receive the intervention. All patients enrolled in the CBT for AUD program consent for their anonymous data to be used for program evaluation. Non-consenting patients will not be included in the dataset but will receive the intervention. Participation is voluntary and patients may withdraw a any time without penalty. Patients who do not achieve abstinence will be offered ongoing support or referral options appropriate to their condition and circumstances. Patient outcomes post the 3-month treatment period will not be included in this study.
Intervention code [1] 314009 0
Behaviour
Intervention code [2] 314010 0
Treatment: Other
Intervention code [3] 314011 0
Lifestyle
Comparator / control treatment
Historical control of AH patients referred to the Cognitive-Behavioural Therapy (CBT) program for Alcohol Use Disorder (AUD; Treatment as Usual, TAU) from 01/01/2012 to 01/01/2019. TAU is not manualised or based on specific guidelines. Clinical psychologists are trained in administration of CBT for AUD.
Control group
Historical

Outcomes
Primary outcome [1] 319741 0
Patient retention as determined by the percentage of patients engaged in treatment at each time point.
Timepoint [1] 319741 0
Each of 8 sessions across 12-week intervention. Time points are non-standard, though will typically occur at 7-14 day intervals.
Secondary outcome [1] 369360 0
Percentage of days alcohol is consumed between sessions. Drinking days are determined by a Time-Line Follow Back procedure conducted by psychologists during each session.
Timepoint [1] 369360 0
Each of 8 sessions across 12-week intervention. Time points are non-standard, though will typically occur at 7-14 day intervals.
Secondary outcome [2] 370317 0
Patient engagement as determined by the proportion of patients offered the CBT for AUD program who commence treatment relative to those who do not.
Timepoint [2] 370317 0
Timepoint 1: Pre-treatment assessment.
Timepoint 2: Session 1.
Time between pre-treatment assessment and session 1 is non-standard.

Eligibility
Key inclusion criteria
All Alcoholic Hepatitis (AH) patients will be diagnosed and medically managed by liver disease specialists (Hepatologists) and Addiction specialist. Liver biopsy remains the gold standard for diagnosis, however indications for physician practice varies. While biopsy is the preferred inclusion criterion, absence will not be an exclusion criterion. For patients without liver biopsy, inclusion requires 1). Consistent alcohol risk history, 2). Absence of other acute liver injury risk; 3) at least 2/3 of: jaundice < 8 weeks, AST/ALT ratio > 2; neutrophilia. Further characterised on AH severity (Maddrey Discriminant Function 32) and the presence of cirrhosis.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
As this is an effectiveness study all patients eligible for enrolment in the hospital based program will be included. Such eligibility requires patients to be able to provide written informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be unaware of updates to routine care. All patients will effectively receive the active treatment condition.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Historical controls.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome will be assessed via logistic regression, where the outcome is completed treatment (0 = no, 1 = yes) and the independent variable is treatment group (0 = old protocol, 1 = new protocol). Potential confounding variables will be included as covariates (e.g. dependence severity). Depending on the distribution of the number of sessions attended, parametric or non-parametric statistics may be employed to determine whether more sessions were attended on average. Again, potential confounding variables will be included as covariates. Analysis of secondary secondary outcomes (drinking behaviour) will be analysed using non-parametric longitudinal mixed effects models (Multilevel Modelling). LME models are considered the gold standard in psychotherapy research as they have the advantage of modelling the trajectory of longitudinal outcomes. Missing data may therefore be imputed based on individual trajectories.

To determine non-inferiority or superiority of the new treatment protocol when the primary outcome is patient retention non-inferiority requirements were calculated in R version 3.5.0. Holding power level at 80% and alpha at 0.05, with a present response rate for patients with AH completing treatment at 30% and a modest protocol goal of 40%, a sample size of 70 patients is required to support non-inferiority within a 10% equivalence margin. Given that we have historical data for N ~130 patients, we only require 35 (70 / 2 = 35) patients to commence the new protocol for this study to be sufficiently powered.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13617 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 26279 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 302298 0
Government body
Name [1] 302298 0
Metro South Health Centres for Health Research
Address [1] 302298 0
Metro South Health Research Support Coordinator and Grants Administration Office
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country [1] 302298 0
Australia
Primary sponsor type
Government body
Name
Metro South Health
Address
Metro South Health Research Support Coordinator and Grants Administration Office
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 302571 0
None
Name [1] 302571 0
Address [1] 302571 0
Country [1] 302571 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302973 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 302973 0
Metro South Health HREC
Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 302973 0
Australia
Date submitted for ethics approval [1] 302973 0
18/04/2019
Approval date [1] 302973 0
Ethics approval number [1] 302973 0

Summary
Brief summary
Alcoholic hepatitis (AH) poses a significant burden on public tertiary hospitals. Medication for AH has recently been demonstrated to be ineffective in a large high-quality study. Sustained alcohol abstinence is the strongest predictor of long-term survival. Behavioural interventions to promote abstinence in AH have not been systematically assessed. We propose to trial an early and intense Cognitive Behavioural Therapy (CBT) program for patients at high risk of poor outcome of alcohol-related liver disease/severe AH and evaluate treatment outcome as a matter of quality assurance.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92030 0
Prof Jason Connor
Address 92030 0
Alcohol and Drug Assessment Unit
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road, Woolloongabba Queensland 4102
Country 92030 0
Australia
Phone 92030 0
+61 07 31765191
Fax 92030 0
Email 92030 0
jason.connor@health.qld.gov.au
Contact person for public queries
Name 92031 0
Dr Jason Coates
Address 92031 0
Alcohol and Drug Assessment Unit
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road, Woolloongabba Queensland 4102

Country 92031 0
Australia
Phone 92031 0
+61 07 3176 5191
Fax 92031 0
Email 92031 0
jason.coates@health.qld.gov.au
Contact person for scientific queries
Name 92032 0
Dr Jason Coates
Address 92032 0
Alcohol and Drug Assessment Unit
Princess Alexandra Hospital | Metro South Health
199 Ipswich Road, Woolloongabba Queensland 4102
Country 92032 0
Australia
Phone 92032 0
+61 07 3176 5191
Fax 92032 0
Email 92032 0
jason.coates@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Clinical study report
Ethical approval
How or where can supporting documents be obtained?
Type [1] 1860 0
Ethical approval
Citation [1] 1860 0
Link [1] 1860 0
Email [1] 1860 0
Other [1] 1860 0
Pending ethics approval (11/4/19). Available upon request
Attachment [1] 1860 0
Summary results
No Results