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Trial registered on ANZCTR


Registration number
ACTRN12623000397617
Ethics application status
Approved
Date submitted
24/01/2023
Date registered
19/04/2023
Date last updated
21/06/2024
Date data sharing statement initially provided
19/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Temporary Withholding of Immunosuppressant in Rheumatic diseases and Lupus (TWIRL) Study
Scientific title
Change in Anti-Influenza Antibody Level following Temporary Withholding of Immunosuppressant in Rheumatic diseases and Lupus (TWIRL) Study
Secondary ID [1] 308823 0
None
Universal Trial Number (UTN)
Trial acronym
TWIRL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic lupus erythematosus 328781 0
Condition category
Condition code
Inflammatory and Immune System 325788 325788 0 0
Autoimmune diseases
Inflammatory and Immune System 325789 325789 0 0
Connective tissue diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Temporary withholding of mycophenolate for 2 weeks after vaccination. The dose will depend on the usual dose that patient is currently receiving, which can vary usually between 500mg twice daily to 1.5g twice daily orally. We will be relying on text messages and emails to remind participants to resume to taking their medications.
We will be offering participants the standard influenza vaccine as eligible for patients who have impaired immunity as part of the National Immunisation Program. For those who participated in 2023, we offered the Afluria Quad (CSL Sequirus) influenza vaccination. In 2024, we will offer an equally appropriate influenza vaccine of those available as part of the National Immunisation Program - the Flucelvax Quad (CSL Sequirus) influenza vaccination.
Intervention code [1] 325271 0
Treatment: Drugs
Comparator / control treatment
Control arm is usual care which is to continue immunosuppressant as per usual
Control group
Active

Outcomes
Primary outcome [1] 333632 0
Proportion of patients achieving greater than 4-fold increase in antibody titre of Anti-influenza antibody in plasma by haemagglutination inhibition assay (HIA) in 2 of 4 influenza vaccine antigens compared to baseline
Timepoint [1] 333632 0
Bloods collected at baseline (week 0) and 4 weeks following vaccination will be analysed to measure change in HIA
Secondary outcome [1] 417812 0
Patient flares will be assessed via both physician-reported and patient-reported measures. A patient-reported outcome measure in the form of RAPID3 (score 0-30) will be captured, with a flare defined as a RAPID3 score of greater than or equal to 13.
Timepoint [1] 417812 0
Participants will be asked to complete the RAPID3 questionnaire at five timepoints: at baseline (week 0), week 2, 4, 8, and 12 following influenza vaccine.
Secondary outcome [2] 420436 0
Flares will also be captured by SFI (SLE Flare Index), a physician-reported measurment
Timepoint [2] 420436 0
SFI will be assessed at baseline (week 0) and at a lupus clinic visit 5 weeks following influenza vaccine.
Secondary outcome [3] 420437 0
Flare assessment by physician using the Physicians' Global Assessment (PGA), where a flare is defined as a change of 1 or greater from baseline.
Timepoint [3] 420437 0
PGA will be assessed at baseline (week 0) and at a lupus clinic visit 5 weeks following influenza vaccine.

Eligibility
Key inclusion criteria
• Patients with systemic lupus erythematosus, who are currently enrolled in the Australian Lupus Registry & Biobank.
• Receiving stable doses of mycophenolate and have not experienced a flare in the last 3 months.
• Combination with hydroxychloroquine will be permitted
• Prednisolone must be at a dose equal or lower than 7.5mg/day.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Concomitant use of other biologics such as rituximab or belimumab in the last 6 months
• Other targeted synthetic disease modifying anti-rheumatic drugs such as JAK inhibitors
• Age >65 as a different, adjuvated vaccine is clinically recommended for this age group

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 will be carried out through randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
No new medication is being trialled. This study aims to investigate the effect of withholding mycophenolate in SLE patients for two weeks after patients receive an influenza vaccine. Patients will be randomised to either Group 1: withholding mycophenolate for two weeks or Group 2: continuing mycophenolate use per normal
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Satisfactory vaccine response to seasonal influenza vaccination will be defined by greater than or equal to a four-fold increase in antibody titre in two of four influenza vaccine antigens compared to baseline responses prior to immunization. The proportion of participants who achieve a satisfactory vaccine response from each group will be reported and compared, using Fisher’s exact test. Other continuous variables are analysed by using a t-test or Mann Whitney U test as appropriate. Binary secondary efficacy variables (such as frequency of disease flare and incidence of infection) will be compared using Fisher’s exact test. Logistic regression will be used to assess the association of clinical variables such as absolute B-cell and/or T-cells numbers at baseline, study group assignment (temporary interruption vs continuation), and other disease-related parameters with adequate vaccine response. P<0.05 is considered to indicate statistical significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
24/04/2023
Actual
16/05/2023
Date of last participant enrolment
Anticipated
31/08/2024
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
80
Accrual to date
19
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24473 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 39340 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 313046 0
University
Name [1] 313046 0
Monash University
Country [1] 313046 0
Australia
Funding source category [2] 313582 0
Charities/Societies/Foundations
Name [2] 313582 0
Arthritis Australia
Country [2] 313582 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Monash Health
246 Clayton Road
Clayton 3168
Victoria
Country
Australia
Secondary sponsor category [1] 314733 0
University
Name [1] 314733 0
Monash University
Address [1] 314733 0
School of Clinical Science
246 Clayton Road
Clayton 3168
Victoria
Country [1] 314733 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312299 0
Monash Health HREC
Ethics committee address [1] 312299 0
Research Support Services
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
Clayton VIC 3168
Ethics committee country [1] 312299 0
Australia
Date submitted for ethics approval [1] 312299 0
15/11/2022
Approval date [1] 312299 0
10/02/2023
Ethics approval number [1] 312299 0

Summary
Brief summary
Mycophenolate is an immunosuppressant that is widely used as a treatment for systemic lupus erythematosus (SLE). Its biological effects involve a reduction in immune cell functions, which in turn reduce systemic or organ related inflammation and damage. The benefits of using mycophenolate in SLE need to be carefully balanced against unintended side effects such as increased risk of infection or blunting of vaccine responses. One strategy to counteract these effects is the temporary withdrawal of the immunosuppressant, which allows for the immune system to recover and effectively respond to a vaccine or infection. Our study will examine the effects of withdrawing mycophenolate for a short period in SLE patients. Our hypothesis is that this temporary withdrawal will result in an improvement in the immune responses to the influenza vaccination while maintaining disease control.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124162 0
A/Prof Alberta Hoi
Address 124162 0
School of Clinical Sciences, Monash Health, 246 Clayton Road, Clayton 3168, Victoria
Country 124162 0
Australia
Phone 124162 0
+61 411145282
Fax 124162 0
Email 124162 0
alberta.hoi@monash.edu
Contact person for public queries
Name 124163 0
A/Prof Alberta Hoi
Address 124163 0
School of Clinical Sciences
246 Clayton Road
Clayton 3168
Victoria
Country 124163 0
Australia
Phone 124163 0
+61 03 9594 4899
Fax 124163 0
Email 124163 0
alberta.hoi@monash.edu
Contact person for scientific queries
Name 124164 0
A/Prof Alberta Hoi
Address 124164 0
School of Clinical Sciences, Monash Health, 246 Clayton Road, Clayton 3168, Victoria
Country 124164 0
Australia
Phone 124164 0
+61411145282
Fax 124164 0
Email 124164 0
alberta.hoi@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?
Upon request, deidentified, pooled data may be shared.
When will data be available (start and end dates)?
For up to 7 years after publication date
Available to whom?
For academic researchers
Available for what types of analyses?
For researchers interested in meta-analyses
How or where can data be obtained?
In writing by email principal investigator alberta.hoi@monash.edu


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18113Study protocol  alberta.hoi@monash.edu 385276-(Uploaded-05-04-2024-11-47-01)-Study-related document.docx
18115Informed consent form  alberta.hoi@monash.edu 385276-(Uploaded-05-04-2024-11-47-29)-Study-related document.pdf
18116Clinical study report  alberta.hoi@monash.edu
18117Ethical approval  alberta.hoi@monash.edu 385276-(Uploaded-05-04-2024-11-49-34)-Study-related document.pdf
18118Analytic code  alberta.hoi@monash.edu



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.