ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

TWIRL

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Systemic lupus erythematosus

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Inflammatory and Immune System

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]

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]

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]

Bloods collected at baseline (week 0) and 4 weeks following vaccination will be analysed to measure change in HIA

Secondary outcome [1]

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]

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]

Flares will also be captured by SFI (SLE Flare Index), a physician-reported measurment

Timepoint [2]

SFI will be assessed at baseline (week 0) and at a lupus clinic visit 5 weeks following influenza vaccine.

Secondary outcome [3]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment postcode(s) [1]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

University

Name [1]

Monash University

Address [1]

School of Clinical Sciences
246 Clayton Road
Clayton Victoria 3168

Country [1]

Australia

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Arthritis Australia

Address [2]

Arthritis Australia
Level 2/255 Broadway
GLEBE NSW 2037

Country [2]

Australia

Primary sponsor type

Hospital

Name

Monash Health

Address

Monash Health
246 Clayton Road
Clayton 3168
Victoria

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Monash University

Address [1]

School of Clinical Science
246 Clayton Road
Clayton 3168
Victoria

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health HREC

Ethics committee address [1]

Research Support Services
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
Clayton VIC 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/11/2022

Approval date [1]

10/02/2023

Ethics approval number [1]

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

A/Prof Alberta Hoi

Address

School of Clinical Sciences, Monash Health, 246 Clayton Road, Clayton 3168, Victoria

Country

Australia

Phone

+61 411145282

Fax

alberta.hoi@monash.edu

Contact person for public queries

Name

Alberta Hoi

Address

School of Clinical Sciences
246 Clayton Road
Clayton 3168
Victoria

Country

Australia

Phone

+61 03 9594 4899

Fax

alberta.hoi@monash.edu

Contact person for scientific queries

Name

Alberta Hoi

Address

School of Clinical Sciences, Monash Health, 246 Clayton Road, Clayton 3168, Victoria

Country

Australia

Phone

+61411145282

Fax

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.	Type	Email	Attachment
18113	Study protocol	alberta.hoi@monash.edu	385276-(Uploaded-05-04-2024-11-47-01)-Study-related document.docx
18115	Informed consent form	alberta.hoi@monash.edu	385276-(Uploaded-05-04-2024-11-47-29)-Study-related document.pdf
18116	Clinical study report	alberta.hoi@monash.edu
18117	Ethical approval	alberta.hoi@monash.edu	385276-(Uploaded-05-04-2024-11-49-34)-Study-related document.pdf
18118	Analytic code	alberta.hoi@monash.edu

Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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