Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000290695
Ethics application status
Approved
Date submitted
2/03/2023
Date registered
17/03/2023
Date last updated
23/02/2024
Date data sharing statement initially provided
17/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
PET/CT as a Diagnostic Test for Polymyalgia Rheumatica
Scientific title
Prospective Validation of 18F-FDG Whole Body PET/CT as a Diagnostic Test for Polymyalgia Rheumatica
Secondary ID [1] 309113 0
None
Universal Trial Number (UTN)
Trial acronym
ProPET
Linked study record
Participating in this study also involves participation in a biobank and registry study called the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC; 2019/PID11585; 2019/ETH10386; ACTRN12621001564842). The A3BC works with the clinical trial team to provide supporting infrastructure for the capture of trial data and biospecimen collection/processing/storage services.

Health condition
Health condition(s) or problem(s) studied:
Polymyalgia rheumatica 329202 0
Condition category
Condition code
Inflammatory and Immune System 326159 326159 0 0
Other inflammatory or immune system disorders
Musculoskeletal 326237 326237 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with suspected polymyalgia rheumatica (PMR) will be recruited and given information (in paper or electronic format) outlining the research project’s purpose, and participant involvement will be provided to eligible patients by a study investigator.

All participants will be eligible for the associated sub-study “Predicting Autoimmunity” as they have an autoimmune rheumatic disease, with participation involving the additional collection of one heparin-containing, one EDTA-containing and one serum gel tube of blood at baseline and the 6-month follow-up visit. No additional time is required to complete this sub-study, as the biomarkers collected will be simply added to the existing biobank.

Following enrolment, a baseline study visit (face-to-face) will be scheduled in the Rheumatology Department at Heidelberg Repatriation Hospital. Morning visits will be arranged (when PMR symptoms are typically at their worst). The estimated duration is 1 hour. The following clinical data will be collected:
1) Demographic: date of birth, sex and race.
2) History: disease onset, distribution of joint involvement (marked on a patient mannequin), severity of pain (Numeric Rating Scale [NRS]), severity (NRS) and duration of early morning stiffness (mins), and presence of constitutional symptoms (loss of weight [kg], fever and fatigue).
3) Examination: vital signs, body mass index, peripheral joint swelling/joint line tenderness and shoulder range of movement (elevation of upper limb score and goniometer degree).
4) Patient-reported outcomes: Visual Analogue Scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), 36-item Short Form Survey (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

In order to generate a PMR-Activity Score (PMR-AS), the study investigator will also complete a Physician Global Score (PGS).

Baseline investigations will comprise:
1) Laboratory: FBE, UEC, LFTs, CRP, ESR, rheumatoid factor, ACPA, ANA, ANCA, CK, TSH, Vitamin D, HbA1C and “Predicting Autoimmunity” samples for novel biomarker testing if opted in;
2) Radiology: x-ray of hands (to assess for erosive change), performed in the Radiology Department at Heidelberg Repatriation Hospital.
3) Whole body PET/CT: within 7 days of enrolment, performed in the Centre for Molecular Imaging and Therapy at the Austin Hospital using the Phillips PET/CT camera. This visit will take approximately 2 hours. Qualitative evaluation of 18F-FDG uptake at those musculoskeletal sites included in the Heidelberg algorithm and concise Leuven/Groningen score (the “simplified” methods for diagnosing PMR) will be undertaken by two experienced Nuclear Medicine Physicians, both of whom will not be privy to additional clinical information and will not require any further training given their experience with these methods.

The Heidelberg algorithm utilises pre-specified qualitative scoring of abnormal 18F-FDG uptake at just three musculoskeletal sites – adjacent to the ischial tuberosities, in combination with either the peri-articular shoulder or interspinous bursa (Owen et al. Abnormalities at three musculoskeletal sites on whole-body positron emission tomography/computed tomography can diagnose polymyalgia rheumatica with high sensitivity and specificity. EJNMMI. 2020;47(10):2461-8).

Participants will complete a standardised symptom and treatment diary at monthly intervals over the 6-month follow-up period.

At 24 weeks post enrolment, a final study visit will be undertaken at Heidelberg Repatriation Hospital (visit duration 30 minutes). This shall comprise the same assessments carried out at baseline and repeat laboratory testing (FBE, UEC, LFTs, CRP, ESR and “Predicting Autoimmunity” samples for novel biomarker testing if opted in). The participant’s final clinical diagnosis will be determined by the treating rheumatologist.
Intervention code [1] 325559 0
Diagnosis / Prognosis
Comparator / control treatment
Clinical diagnosis by 2012 EULAR/ACR Classification Criteria in the same cohort undergoing intervention

(Dasgupta et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012 Apr;71(4):484-92.)
Control group
Active

Outcomes
Primary outcome [1] 334033 0
Sensitivity and specificity of the existing Heidelberg algorithm and concise Henckaerts/Van der Geest score for diagnosing PMR on whole body PET/CT compared to clinical diagnosis as determined by treating rheumatologist
Timepoint [1] 334033 0
At 6 months follow-up (post enrolment)
Secondary outcome [1] 419138 0
Disease activity as determined by the PMR-Activity Score (PMR-AS)
Timepoint [1] 419138 0
At baseline and 24 weeks (post enrolment)

Eligibility
Key inclusion criteria
Suspected new diagnosis of PMR as determined by age at symptom onset greater than or equal to 50 years, bilateral shoulder aching, and elevated CRP and/or ESR (in line with 2012 EULAR/ACR Classification Criteria).
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Inability to provide informed consent.
- Patients with symptoms suggestive of giant cell arteritis (headache, jaw claudication, scalp tenderness and/or visual disturbance).
- Patients with active infection.
- Patients with recent malignancy.
- Patients with established inflammatory rheumatic diseases (e.g. RA).
- Patients with uncontrolled diabetes (due to inability to accurately interpret 18F-FDG uptake).
- Patients who have been treated with glucocorticoids for greater than 7 days prior to screening, a single dose of prednisolone greater than or equal to 30mg/day and concomitant DMARD therapy.

Study design
Purpose of the study
Diagnosis
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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
The target sample size is 60 patients. This was calculated using bootstrap simulation from the Heidelberg algorithm development data, assuming even numbers of PMR and non-PMR patients. This sample size was calculated to provide sufficient statistical power to measure the Heidelberg algorithm sensitivity and specificity with standard deviations =0.05.

Algorithm/score comparison will be performed by comparing sensitivity and specificity using non-inferiority testing, as developed by Liu et al.(19) Exploratory analysis of baseline variables will be conducted using univariable and multivariable regression models with appropriate link functions for binary (e.g. PMR diagnosis) and continuous outcomes (e.g. number of musculoskeletal sites with 18F-FDG uptake).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/03/2023
Actual
6/04/2023
Date of last participant enrolment
Anticipated
1/01/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313314 0
Charities/Societies/Foundations
Name [1] 313314 0
Arthritis Australia
Country [1] 313314 0
Australia
Primary sponsor type
Hospital
Name
Rheumatology Clinical Trials, Austin Health
Address
Level 1, North Wing
Heidelberg Repatriation Hospital
300 Waterdale Road
Heidelberg Heights VIC 3081
Country
Australia
Secondary sponsor category [1] 315059 0
None
Name [1] 315059 0
Address [1] 315059 0
Country [1] 315059 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312538 0
Austin Health HREC
Ethics committee address [1] 312538 0
Ethics committee country [1] 312538 0
Australia
Date submitted for ethics approval [1] 312538 0
Approval date [1] 312538 0
23/11/2022
Ethics approval number [1] 312538 0
HREC/86331/Austin-2022

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

Contacts
Principal investigator
Name 125022 0
Dr Claire Owen
Address 125022 0
Rheumatology Department
Level 1, North Wing
Heidelberg Repatriation Hospital
Heidelberg Heights VIC 3081
Country 125022 0
Australia
Phone 125022 0
+61 394964038
Fax 125022 0
Email 125022 0
claire.owen@austin.org.au
Contact person for public queries
Name 125023 0
Claire Owen
Address 125023 0
Rheumatology Department
Level 1, North Wing
Heidelberg Repatriation Hospital
Heidelberg Heights VIC 3081
Country 125023 0
Australia
Phone 125023 0
+61 394964038
Fax 125023 0
Email 125023 0
claire.owen@austin.org.au
Contact person for scientific queries
Name 125024 0
Claire Owen
Address 125024 0
Rheumatology Department
Level 1, North Wing
Heidelberg Repatriation Hospital
Heidelberg Heights VIC 3081
Country 125024 0
Australia
Phone 125024 0
+61 394964038
Fax 125024 0
Email 125024 0
claire.owen@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the trial after de-identification
When will data be available (start and end dates)?
Following main results publication, no end date
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access subject to approvals by Principal Investigator (claire.owen@austin.org.au)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18462Study protocol  claire.owen@austin.org.au



Results publications and other study-related documents

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

Documents added automatically
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