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Trial registered on ANZCTR


Registration number
ACTRN12625000186459
Ethics application status
Approved
Date submitted
24/01/2025
Date registered
17/02/2025
Date last updated
17/02/2025
Date data sharing statement initially provided
17/02/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
Virtual Clinic model of care as a platform to deliver Values Based Health Care for Inflammatory Bowel Disease patients undertaking dosage intensification of biologic therapies due to secondary loss of response or pharmacokinetic failure.
Scientific title
Prospective parallel cohort study of virtual clinic model of care versus
traditional standard of care in management of patients undertaking dosage intensification of biologic therapies due to secondary loss of response or pharmacokinetic failure.
Secondary ID [1] 313801 0
nil known
Universal Trial Number (UTN)
Trial acronym
VIVA-IBD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
inflammatory bowel disease 336437 0
Condition category
Condition code
Inflammatory and Immune System 332958 332958 0 0
Autoimmune diseases
Public Health 333042 333042 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single tertiary centre that has an established virtual biologics clinic, where enrolled patients are reviewed in their absence with up to date clinical and objective disease assessment, captured through a patient reported outcome monitoring portal, IBD nurse/pharmacist pphone review and standardised objective disease assessment. All patients at the intervention site (Austin Health) that meet inclusion criteria who are deemed appropriate for dosage intensification of their biologic regimen from their baseline dosage and who agree to participate in the study will have their ongoing treatment and assessments outlined via the virtual clinic model. Patients in the standard care cohort will have treatment, monitoring and follow up scheduled by their individual clinician.
Patients in intervention cohort will be managed through protocolised multidisciplinary care, with follow up assessment and virtual clinic review, in addition to TWO in person clinic reviews, scheduled as per the individual needs of the patient and as agreed by the multidisciplinary team including clinician, IBD pharmacist and IBD nurse over the 48 week study timeframe.
There will be no limit on the number of virtual clinic reviews conducted for each patient with rveiews scheduled as per the individual needs of that patient. Patients in both study cohorts will undergo objective and clinical disease assessment at baseline, week 12, week 24 and week 48.
Intervention code [1] 330390 0
Treatment: Other
Comparator / control treatment
Standard of care at a separate tertiary centre without the use of a virtual biologics clinic.
Patients in the standard care cohort will have treatment, monitoring and follow up scheduled by their individual clinician with no restrictions or limitations on the timeframe or frequency of these follow ups.
Control group
Active

Outcomes
Primary outcome [1] 340496 0
Equivalence in clinical disease activity as defined as defined by Harvey bradsaw Index (HBI) > 5 orSimple clinical colitis activity index (SCCAI) > 5 with objective evidence of disease defined as one or more of faecal calprotectin greater than or equal to 150µg/ml, C-reactive protein (CRP) = 5mg/L, and/or documented endoscopy/radiology reports.
Timepoint [1] 340496 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Primary outcome [2] 340582 0
Biochemical disease assessment
Timepoint [2] 340582 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Primary outcome [3] 340583 0
Biochemical Assessment (faecal calprotectin)
Timepoint [3] 340583 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Secondary outcome [1] 444261 0
Total costs of care (direct)
Timepoint [1] 444261 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Secondary outcome [2] 444262 0
Patient Reported Quality of Healthcare delivery
Timepoint [2] 444262 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Secondary outcome [3] 444263 0
Patient reported general health related quality of life - this will be assessed as a composite outcome
Timepoint [3] 444263 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care
Secondary outcome [4] 444264 0
Appropriateness of dose escalation of therapies
Timepoint [4] 444264 0
Baseline only
Secondary outcome [5] 444516 0
Disease related Quality of life
Timepoint [5] 444516 0
Baseline, week 12 , week 24 and week 48
Secondary outcome [6] 444517 0
Total costs of care (indirect)
Timepoint [6] 444517 0
Baseline, week 12, week 24 and week 48 post enrolment in intervention or standard care

Eligibility
Key inclusion criteria
Patients with inflammatory bowel disease (IBD) (Crohn’s disease or Ulcerative colitis) will be recruited from two tertiary, metropolitan IBD centres in Australia (Austin Health, Melbourne and Mater Misericordiae Ltd via outpatient clinics, nurse-led clinics, pharmacist-led outpatient referrals or multidisciplinary meetings. Patients will be enrolled into the study, once their primary treating clinician determines that dosage intensification is required, from standard maintenance dosing or from their maintenance dose at the time of study commencement, due to secondary loss of response or pharmacokinetic failure in the setting of subtherapeutic serum drug levels
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Non-English speaking patients will be excluded due to a fundamental need for accurately completed online questionnaires to determine the impact of the intervention. Limited resources mean that translational assistance will not be available throughout the study duration.

Patients without access to computers/or smartphone devices or who for any other reason would not be able to complete online surveys

People highly dependent on medical care who may be unable to give consent

People with a cognitive impairment and/or intellectual disability

Patients undergoing dosage intensification of there biologic therapy for a severe flare of their IBD where the patient is at high risk of acute deterioration AND is commenced on corticosteroids AND it is the view of the IBD MDT that the patient would not be suitable for ongoing management through the virtual clinic pathway only

Patients whom are discovered to be pregnant and or are imminently planning pregnancy due to the increased monitoring required in this patient population.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
As this is a pilot study, determining the feasibility of this novel approach to IBD service delivery and investigating its utility in being able to deliver a Values based health model, no specific sample sizes and power calculations are able to be calculated. Whilst this is the first study of its kind, a similar study by Srinivasan et al, which assessed the appropriateness of dose intensification and subsequently the clinical outcomes with a virtual model compared to standard of care, achieved statistically significant results (p<0.05) with 149 patients recruited. We envisage that we will be able to obtain meaningful results with a total of 110 patients enrolled. It is anticipated that due to protocol design, patients in the virtual clinic arm are at an increased risk of 'treatment failure' as an active flare of their inflammatory bowel disease whilst no patients in the standard of care arm will be termed a 'treatment failure'. This will likely result in uneven patient number completing the study protocol to 48 weeks. Through an extensive literature review, it is expected that between 10 and 20% of patients on maintenance biologic therapies will have a flare of their IBD in a 12 month period. In order to ensure that similar patient numbers complete the 48 week study protocol, we would like to revise the number of patients recruited into the virtual clinic study arm, conducted at Austin Health to 60 patients, accounting for a 20% 'treatment failure' rate. This amendment in the study protocol will be acknowledged and referenced in the publication of any results concluded from the study.
Data will be assessed descriptively and subjected to Shapiro-Wilk tests. With the help of a biostatistician who has been involved in the development of the study design and study concept. Continuous data will be compared with Mann-Whitney tests, and proportions expressed as percentages and compared using two-sided Fisher’s exact tests. Continuous data will be kept in original form where possible.

Further bivariate analyses will be performed, including Kaplan-Meier survival curves to compare the proportion achieving treatment success and time to objectively assessed disease remission following dose intensification through to end of follow-up across both cohorts with differences assessed by log-rank tests. Subsequently, Cox multivariable regression analysis will be performed, incorporating statistically significant (and those trending towards significant, p<0.10) variables associated with time to treatment success in bivariate analyses, plus factors putatively important in biologic treatment success, including age at time of escalation, sex, disease behaviour and extent, time to commencement of biologic from diagnosis, time since diagnosis, concurrent immunomodulation, markers of inflammatory activity and serum albumin. A forced entry model will be used, with the final model selected on the basis of the Omnibus test of goodness of fit. P-values < 0.05 will be considered significant.

Questionnaires will be assessed using a combination of descriptive and statistical analysis as above. Outcomes of the non-validated questionnaire will be assessed for trends. Trends will highlight discrepancies in the quality of care provision in each arm. Validated questionnaires will have scores aggregated and compared to the validated, accepted ranges designed to demonstrate their particular outcome measure. Results in each arm will be compared using a combination of descriptive and statistical analysis using methods outlined above.

The economic impact of IBD will be totaled and segregated into direct (hospital related costs) and indirect costs (costs incurred by the patient for out-of-pocket expenses, absence from work etc). A comparison will then be made using mean costs to determine the cost effectiveness of the novel model of care compared to current standard of care.

Economic analysis

We will use data from our prospective cohort study to derive an outcome that also represents a measure of value. However, there is currently no clear outcome measure that defines value in IBD. Therefore, we will define the value proposition of a VBHC model of care by concurrently undertaking a traditional Cost Utility Analysis which divides costs by incremental health improvement to report Quality Adjusted Life Years (QALY). QALYs will be calculated by determining the impact that IBD has on each participant’s quality of life (QoL). We aim to measure health related quality of life (HRQoL) using the EQ-5D-5L and will map these findings to an IBD specific quality of life measurement tool (sIBDq) using regression equations. The monetary value saving achieved per patient in the intervention arm which will then be compared to established Australian thresholds eg $50,000 per QALY achieved to determine the cost effectiveness of the intervention. Regression mapping of sIBDq and EQ-5D-5L has not been conducted previously however the longer form version of sIBDq, IBDQ, have been shown to correlate and we anticipate a similar outcome. We will assess the costs of delivering the VBHC and potential off-sets in relation to savings and cost-avoidance by way of emergency visits, and hospitalisation, according to the standard National Weighted Activity Units. Cost of the intervention will be determined by calculating a monetary value saving achieved per patient in the intervention arm relative to the control arm. An incremental cost effectiveness ratio (ICER) will be calculated using the formula:

Cost (intervention) – Cost (comparator) / Outcomes (intervention – Outcomes (comparator)

This will in turn allow us to make an evaluation of the value of this model of care delivery and assess its ability to help achieve VBHC. It will also incorporate savings in indirect costs incurred by patients which are hypothesised to be substantially higher than the direct costs.

Bias will be minimised by ensuring enrolment of all patients undergoing escalation across each site, minimising the risks of selection bias. Patients may only avoid enrolment if consent is not provided, or permission is granted on the basis of clinical/ethical grounds by the lead site primary investigator.

The highly protocolised, multidisciplinary format of the VBC study arm will minimise variability in care provision and reduce risk of individual clinician bias. Conversely, the SOC arm, with no protocolised interventions we hypothesise will highlight high variability in individual clinicians prescribing practices in managing this difficult to treat cohort.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
19/10/2023
Date of last participant enrolment
Anticipated
5/01/2026
Actual
Date of last data collection
Anticipated
7/12/2026
Actual
Sample size
Target
110
Accrual to date
53
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 27520 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 27521 0
Mater Hospital Brisbane - South Brisbane
Recruitment postcode(s) [1] 43632 0
3084 - Heidelberg
Recruitment postcode(s) [2] 43633 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 318268 0
Commercial sector/Industry
Name [1] 318268 0
J&J Innovative Medicine
Country [1] 318268 0
Australia
Primary sponsor type
Hospital
Name
Austin Health Hospital
Address
Country
Australia
Secondary sponsor category [1] 320655 0
Hospital
Name [1] 320655 0
Mater Hospital
Address [1] 320655 0
Country [1] 320655 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316908 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 316908 0
Ethics committee country [1] 316908 0
Australia
Date submitted for ethics approval [1] 316908 0
01/05/2023
Approval date [1] 316908 0
08/08/2023
Ethics approval number [1] 316908 0
HREC/91516/Austin-2023
Ethics committee name [2] 316909 0
Mater Misericordiae Ltd Human Research Ethics Committee
Ethics committee address [2] 316909 0
Ethics committee country [2] 316909 0
Australia
Date submitted for ethics approval [2] 316909 0
12/02/2024
Approval date [2] 316909 0
13/09/2024
Ethics approval number [2] 316909 0
91516

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

Contacts
Principal investigator
Name 139398 0
Prof Peter De Cruz
Address 139398 0
Austin Health, 145 Studley Road, Heidelberg, VIC 3084
Country 139398 0
Australia
Phone 139398 0
+61 394965717
Fax 139398 0
Email 139398 0
peter.decruz@austin.org.au
Contact person for public queries
Name 139399 0
Mr Patrick Hilley
Address 139399 0
Austin Health, 145 Studley Road, Heidelberg, VIC 3084
Country 139399 0
Australia
Phone 139399 0
+61 394966847
Fax 139399 0
Email 139399 0
patrick.hilley@austin.org.au
Contact person for scientific queries
Name 139400 0
Mr Patrick Hilley
Address 139400 0
Austin Health, 145 Studley Road, Heidelberg, VIC 3084
Country 139400 0
Australia
Phone 139400 0
+61 394966847
Fax 139400 0
Email 139400 0
patrick.hilley@austin.org.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?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.