Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001703897
Ethics application status
Approved
Date submitted
10/11/2021
Date registered
13/12/2021
Date last updated
25/06/2024
Date data sharing statement initially provided
13/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A home-based, multidisciplinary liver optimisation program for the first 28 days after an admission for acute-on-chronic liver failure (LivR Well)
Scientific title
A home-based, multidisciplinary liver optimisation program for the first 28 days after an admission for acute-on-chronic liver failure (LivR Well)
Secondary ID [1] 305763 0
Nil known
Universal Trial Number (UTN)
U1111-1271-3769
Trial acronym
LivR Well
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cirrhosis 324265 0
acute-on-chronic liver failure 324266 0
Condition category
Condition code
Oral and Gastrointestinal 321761 321761 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The 28 day intervention will be delivered through ‘Hospital in the Home’ (HITH), a medically-led ambulatory care program supported by physical clinics and home-visits by the nursing team. HITH is able to deliver many aspects of acute hospital care in the community, for otherwise stable patients. This includes diagnosis and management of acute conditions that would typically require bed-based care
Patients will have access to up to three, 1 hour home visits per week by nursing staff and physiotherapists. Nursing aspects of the home visits will include routine vital sign assessment (heart rate, respiratory rate, blood pressure, pulse oximetry and temperature), blood tests requested by medical staff (full blood count, urea/creatinine/electrolytes, liver function tests, international normalised ratio), administration of quality of life assessments at baseline/week 6/week 12 (Chronic Liver Disease Questionnaire and EuroQoL 5D), and general enquiry regarding concerns and wellbeing. Nursing staff can escalate to medical staff whenever a concern is raised. The patients will attend a hospital-based ambulatory care liver clinic weekly, for up to 2 hours duration, for a medical and nursing review with dietitian, social work, addiction medicine specialists and pharmacist consultations as required. Patients could be referred to LivR Well from an outpatient context, the emergency department or the inpatient ward. All severity of liver disease is eligible unless the patient is receiving end of life care. There are no cut-offs for MELD score or Child Turcotte Pugh score.
The intervention will be personalised to the patient based on the criteria below. Intervention adherence will be assessed by attendance at scheduled appointments and undertaking of investigations requested. Adherence will be monitored on a central database and strategies used to improve fidelity will include direct contact with patients by the hepatology research nurse.
Physiotherapy is indicated if diagnosed with sarcopenia, had a fall in last 6 months or standardised falls risk assessment score suggests increased falls risk. Exercises prescribed will be tailored to individual patients but include falls risk reduction exercises to be performed across up to 3x 60 minute sessions, for the duration of the intervention. Exercises will include those designed for balance training eg alternate leg weight bearing and those designed for sarcopenia eg seated chair push ups. The exercises will be tailored at the discretion of the treating physiotherapist. Outcomes will be assessed using the 6 minute walk test at baseline and day 28
Dietitian is indicated if diagnosed with sarcopenia, diabetes, alcohol dependence and/or a standardised malnutrition risk assessment score suggests malnutrition. Tasks will include implementing a personalised high protein, low salt diet plan including a late-evening snack
Social Work is indicated if the patient requires long term home support services, has an established disability or is aged >65 years. Tasks will include referral for council services, aged care assessment
Neuropsychiatry assessment is indicated if there is concern from the medical team regarding cognition outside potentially treatable hepatic encephalopathy. This assessment will not result in provision of therapies but may enable the patient longer term access to appropriate support services including the National Disability Support Scheme.
A pharmacist review is indicated if the patient takes at least 5 different medications regularly (polypharmacy) and/or requires titration of diuretic or lactulose doses
Intervention code [1] 322165 0
Treatment: Other
Comparator / control treatment
The comparator will be outpatient management in a ‘complex care liver clinic’, an ambulatory care clinic for patients with decompensated cirrhosis, promoting continuity of care by a gastroenterologist, hepatology nurse and pharmacist through regular face-to-face appointments. The control cohort will have no access to the additional allied health clinicians, technology aids or home visits through the LivR Well program.
Control group
Active

Outcomes
Primary outcome [1] 329510 0
Primary composite outcome: death, waitlisting for liver transplantation or 30-day readmission. This outcome will be assessed through access to the electronic health record for the health service. This is a multi-site service spanning 3 tertiary centres, secondary hospitals and a catchment of more than 1 million people in south-east Victoria. For patients referred to the statewide liver transplant service, this outcome will be assessed by directly requesting medical records.
Timepoint [1] 329510 0
90 days post-intervention commencement
Primary outcome [2] 338637 0
30-day readmission rate. Admissions and costs data from hospital finance department and clinical data from review of medical records.
Timepoint [2] 338637 0
Primary outcome [3] 338638 0
30-day readmission rate. Admissions and costs data from hospital finance department and clinical data from review of medical records.
Timepoint [3] 338638 0
30 days from commencement of program
Secondary outcome [1] 402801 0
Changes in liver disease severity using Model-for-Endstage-Liver Disease Score (MELD)
Timepoint [1] 402801 0
90 days post-intervention commencement
Secondary outcome [2] 402802 0
Quality of life using CLDQ
Timepoint [2] 402802 0
90 days post-intervention commencement
Secondary outcome [3] 402803 0
Cost-effectiveness compared to standard care. This will be assessed with a cost-effectiveness analysis to demonstrate absolute difference using admissions (including Hospital in the Home) data from hospital finance record reflecting cost to the healthcare system. Further economic assessment using the Incremental Cost Effectiveness Ratio and quality adjusted life years will be undertaken
Timepoint [3] 402803 0
90 days post-intervention commencement
Secondary outcome [4] 403574 0
Changes in liver disease severity using Child-Turcotte-Pugh score
Timepoint [4] 403574 0
90 days post-intervention commencement
Secondary outcome [5] 403575 0
Changes in quality of life using EuroQoL 5D
Timepoint [5] 403575 0
90 days post-intervention commencement

Eligibility
Key inclusion criteria
Adult patients
Acute hepatic decompensation characterised by ascites, variceal haemorrhage, hepatorenal syndrome, hepatic encephalopathy, jaundice
Diagnosis of acute-on-chronic liver failure (ACLF) using the European Foundation of the Study of Liver Failure using the Chronic Liver Failure criteria (EF-CLIF) and which includes age and white cell count. Severity is graded according to the number of organ failures
Requiring consultation from at least 3 allied health clinicians
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Greater than grade 2 hepatic encephalopathy
• Severe chronic extrahepatic disease
• Human immunodeficiency virus (HIV) or ongoing immunosuppressive treatments
• Admission for scheduled procedure or treatment
• Moribund or receiving end-of-life care
• Active malignancy including hepatocellular carcinoma
• Receiving regular albumin infusions for treatment of chronic hepatorenal syndrome (excluding those for periprocedural circulatory support following large volume paracentesis)
• Refractory ascites managed with a intra-peritoneal catheter in-situ
• Inability to provide informed consent
• Residing outside the local hospital service catchment or deemed ineligible for home visits due to staff safety or occupational hazard concerns
• Residing in a residential aged care facility

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will occur as eligibility will be confirmed by the treating medical doctor prior to randomisation by the CLD nurse specialist or research assistant
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be computer randomised and informed of their allocation by the CLD nurse specialist or research assistant prior to discharge or within 24 hours of obtaining informed consent.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Patients will be screened against inclusion and exclusion criteria at the time of diagnosis of ACLF. Those who meet criteria will be enrolled into the study and provide informed consent. These recruited patients will be randomised in a 1:1 ratio to either the LivR Well program or to standard ambulatory care. Participants will be computer randomised and informed of their allocation by the CLD nurse specialist prior to discharge or within 24 hours of obtaining informed consent. Patients from both study arms will be registered on the Virtual Hospital masterlog through Microsoft Power Apps program. Due to the nature of the intervention, blinding of study participants or clinical staff administering the LivR Well program will not be possible. However, outcome ascertainment for the primary outcome, as well as the health services utilisation secondary outcomes will be blinded. Furthermore, all data analyses will be undertaken in a blinded manner. The statistician will be blinded to the feasibility study data results and the treatment allocation of the RCT.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The data analysis for the primary composite endpoint of death, referral for liver transplantation or 30 day readmission from date of hospital discharge will be undertaken on an intention-to-treat basis. A 28 day mortality rate will be calculated from the date of randomisation. For the primary and other binary outcomes, chi-squared tests will be used to compare the intervention and control groups. Survival analyses will also be undertaken, with generation of Kaplan-Meier curves and Cox regression analyses to derive (adjusted) hazard ratios. For continuous outcomes, t-tests or non-parametric equivalents (e.g., Mann-Whitney tests) will be applied to compare the intervention and comparator groups. If key confounders (such as age, sex and comorbidities) are found to be different between the intervention and control groups, these will be controlled for in adjusted analyses. A p value of 0.05 is considered significant and 95% confidence intervals will be reported for all effect estimates A subgroup analysis comparing groups by source of referral will be conducted to address bias created following randomisation whereby in-patients in the intervention arm may be discharged home earlier due to perceived safety with regular home visits compared to those in the control arm with standard ambulatory care. The subgroup analysis will account for differences between those admitted from in-patient admission compared to the emergency department or the ambulatory liver clinic. Another subgroup analysis will be performed for re-enrolment to LivR Well after drop out due to unplanned re-admission to hospital. Data from the first enrolment to LivR Well will be included in the primary outcomes on the intention-to-treat basis. Analyses will be performed using Stata statistical software, version 16.1 for Mac (StataCorp, College Station, Texas, USA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/01/2022
Actual
16/02/2022
Date of last participant enrolment
Anticipated
30/06/2022
Actual
30/04/2024
Date of last data collection
Anticipated
30/09/2022
Actual
30/04/2024
Sample size
Target
94
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 21067 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 21068 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [3] 21069 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 35917 0
3168 - Clayton
Recruitment postcode(s) [2] 35918 0
3175 - Dandenong
Recruitment postcode(s) [3] 35919 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 310122 0
Hospital
Name [1] 310122 0
Monash Health
Country [1] 310122 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Rd, Clayton, Victoria, 3168
Country
Australia
Secondary sponsor category [1] 311197 0
None
Name [1] 311197 0
Address [1] 311197 0
Country [1] 311197 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309810 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 309810 0
Ethics committee country [1] 309810 0
Australia
Date submitted for ethics approval [1] 309810 0
24/05/2021
Approval date [1] 309810 0
31/05/2021
Ethics approval number [1] 309810 0
ERM Reference No. 76264

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115466 0
A/Prof Suong Le
Address 115466 0
Department of Gastroenterology and Hepatology, Level 3, 246 Clayton Rd, Clayton, Victoria, 3168
Country 115466 0
Australia
Phone 115466 0
+61 3 9594 3177
Fax 115466 0
+61 3 9594 6250
Email 115466 0
suong.le@monashhealth.org
Contact person for public queries
Name 115467 0
Natalie Ngu
Address 115467 0
Department of Gastroenterology and Hepatology, Level 3, 246 Clayton Rd, Clayton, Victoria, 3168
Country 115467 0
Australia
Phone 115467 0
+61 3 9594 3177
Fax 115467 0
+61 3 9594 6250
Email 115467 0
natalie.ngu@monash.edu
Contact person for scientific queries
Name 115468 0
Natalie Ngu
Address 115468 0
Department of Gastroenterology and Hepatology, Level 3, 246 Clayton Rd, Clayton, Victoria, 3168
Country 115468 0
Australia
Phone 115468 0
+61 3 9594 3177
Fax 115468 0
+61 3 9594 6250
Email 115468 0
natalie.ngu@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data underlying published results
When will data be available (start and end dates)?
Immediately after publication with no end-date
Available to whom?
Case-by-case basis on request
Available for what types of analyses?
Case-by-case basis on request
How or where can data be obtained?
Subject to approval by Principal Investigator A/Prof Suong Le
Email: suong.le@monashhealth.org


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
14042Study protocol    Following publication
14043Statistical analysis plan    Following publication
14044Informed consent form    Following publication
14045Ethical approval    Attached document 383102-(Uploaded-10-11-2021-20-12-12)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA home-based, multidisciplinary liver optimisation programme for the first 28 days after an admission for acute-on-chronic liver failure (LivR well): a study protocol for a randomised controlled trial.2022https://dx.doi.org/10.1186/s13063-022-06679-x
N.B. These documents automatically identified may not have been verified by the study sponsor.