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Trial registered on ANZCTR


Registration number
ACTRN12620001185954p
Ethics application status
Submitted, not yet approved
Date submitted
7/09/2020
Date registered
9/11/2020
Date last updated
9/11/2020
Date data sharing statement initially provided
9/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of anakinra therapy on cardiovascular risk in acute gout patient
Scientific title
Cardiovascular Risk in Gout and Effect of anti - IL1ß therapy (and usual care) on progression of non-calcified coronary plaque burden (NCB) and high-risk plaques (HRPs) using Cardiac Computer Tomography Angiogram (CCTA) in acute gout
Secondary ID [1] 302238 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gout 318950 0
Cardiovascular disease 318951 0
Condition category
Condition code
Musculoskeletal 316921 316921 0 0
Other muscular and skeletal disorders
Cardiovascular 316922 316922 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The exposure is an attack of acute gout. Patients will randomised to receive anakinra plus allopurinol escalation therapy versus standard care alone. Standard care involves usual acute gout management (colchicine 500mcg daily for duration of flare) plus allopurinol escalation. Allopurinol dose will be increased according to published protocols starting at 50-100mg daily and increased 50-100mg every 2-4 weeks until target uric acid levels are achieved. Target uric level is either 0.30 or 0.36umol/L depending on patient factors (ACR 2020 and EULAR 2016 gout management guidelines). The dose of anakinra will be 100mg daily for 3 days administered subcutaneously and will be administered in clinic.

At baseline, all patients will undergo a Coronary CT Angiogram to assess for plaque burden in coronary arteries which will be repeated at 9 months. We undertake also patient questionnaires, metrology(swollen and tender joint count) and blood tests. The total duration of follow-up for each patient is 9 months.

Patients will be assessed monthly (initial and final visit may last one hour where as other visits approximately 20 mins)
Intervention code [1] 318528 0
Diagnosis / Prognosis
Intervention code [2] 318796 0
Treatment: Drugs
Comparator / control treatment
The group will be observed prospectively. The anakinra group (100mg OD S/C for 3 days) will be compared against the group receiving usual care (comparator group).

In addition, the group receiving usual care alone will be split at the end of the study into a high risk cohort (those who experienced flares during titration of allopurinol therapy as part of usual care) versus low risk cohort (no flares).
Control group
Active

Outcomes
Primary outcome [1] 325031 0
To determine the effect of therapy with an anti-IL-1ß biologic on high-risk rupture prone plaque burden (HRPs) using Cardiac Computer Tomography Angiogram (CCTA) in patients with acute gout.

Timepoint: Baseline and 9 months post enrolment
Timepoint [1] 325031 0
Baseline and 9 months post enrolment
Primary outcome [2] 325373 0
Determine the effect of therapy with an anti-IL-1ß biologic on non-calcified coronary plaque burden (NCB) using Cardiac Computer Tomography Angiogram (CCTA)
Timepoint [2] 325373 0
Baseline and 9 months post enrolment
Secondary outcome [1] 386590 0
Serum assay hs-CRP
Timepoint [1] 386590 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [2] 386591 0
Serum assay 1L-1R level
Timepoint [2] 386591 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [3] 386625 0
Ultrasound inflammation in peripheral joints (hands, wrists, feet, ankles)
Timepoint [3] 386625 0
Baseline and 9 months post enrolment
Secondary outcome [4] 386626 0
Serum assay ESR
Timepoint [4] 386626 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [5] 386627 0
Metrology: this is swollen and tender joint count
Timepoint [5] 386627 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [6] 386628 0
Patient reported pain and gout concerns using Gout Assessment Questionnaire 2.0
Timepoint [6] 386628 0
Baseline and 9 months post enrolment
Secondary outcome [7] 386629 0
Gout flare: using the definition described in the following reference: Gaffo AL, Dalbeth N, Saag K, et al. Validation of a Definition for Flare in Patients with Established Gout [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). The definition requiring fulfillment of at least 3 of 4 criteria (patient-defined gout flare, pain at rest score of >3 on a 0-10-point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint)
Timepoint [7] 386629 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [8] 386630 0
Patient reported pain scores using Patient Global VAS.
Timepoint [8] 386630 0
Baseline, 48 hours post intervention, monthly and 9 months post enrolment
Secondary outcome [9] 386632 0
Painful joints, Using a questionnaire which asks the participants to identify which joints are painful.
The tool is comonly used, and generally called a "painful joint count" based on the 68 joints of the Richie articular index, and uses a homunculous to as shown here: http://www.pmmonline.org/doctor/approach-to-clinical-assessment/examination/describing-joints
Timepoint [9] 386632 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [10] 386633 0
Functional status using Health Assessment Questionnaire (HAQ)
Timepoint [10] 386633 0
Baseline, monthly and 9 months post enrolment
Secondary outcome [11] 387701 0
Efficacy of anakinra using patient pain visual analogue score (VAS).
Timepoint [11] 387701 0
Baseline and 48 hours post intervention.
Secondary outcome [12] 387702 0
Safety and tolerability of anakinra using clinical visit information and adverse event recording.
Timepoint [12] 387702 0
Baseline, monthly and 9 months post enrolment

Eligibility
Key inclusion criteria
A diagnosis of gout according to 2015 ACR criteria and defined clinically as requiring initiation or currently on allopurinol therapy.
45 years and a minimum of 2 risk factors, i.e. controlled hypertension, controlled diabetes, controlled dyslipidemia, obesity, age >55 years, smoker <65 years and first degree relative with evidence of atherosclerosis <65 years will be recruited.
The above cardiac risk factors ensure patients that are likely to have coronary atherosclerotic plaque on CCTA.
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Other forms of inflammatory arthritis (especially rheumatoid arthritis and psoriasis). 2. Moderate to severe hepatic impairment 3. Contra indication to allopurinol, especially azathioprine or 6-mercaptopurine use. 4. Contra indication to anti IL-1 therapy, including active infection (HIV, tuberculosis, hepatitis B or C). 5. Pregnancy or breastfeeding. 6. Presence of any serious medical illness that may preclude follow up. 7. Inability to provide informed consent. 8. eGFR less than 50. 9. Cardiac stents in situ or coronary artery bypass grafts (CABG). 10. Poorly controlled diabetes. 11. Current malignancy.

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)
Pharmacy will create a randomisation table for the administration of anakinra.
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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
No pilot data is available to power this study, so a pragmatic decision has been made to include 14 patients to generate pilot data, assuming 50% will flare on allopurinol initiation. Descriptive statistics (such as mean with standard deviations for continuous variables, frequencies with percentages for categorical variables) will be used to summarise the two study groups. The differences between the study groups will be compared using paired t-test for continuous variables and chi-square tests for categorical variables.

Two investigators will administer the medication and conduct safety assessments. One investigator will be assessing outcomes and will be blinded to the intervention.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/12/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 17438 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 31167 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 306662 0
Charities/Societies/Foundations
Name [1] 306662 0
Spinnaker Health Research Foundation
Country [1] 306662 0
Australia
Primary sponsor type
Hospital
Name
Fiona Stanley Hospital
Address
11 Robin Warren Drive
Murdoch
Western Australia
6150
Country
Australia
Secondary sponsor category [1] 307210 0
None
Name [1] 307210 0
Address [1] 307210 0
Country [1] 307210 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 306842 0
South Metropolitan Health Service Human Research Ethics Committe
Ethics committee address [1] 306842 0
Ethics committee country [1] 306842 0
Australia
Date submitted for ethics approval [1] 306842 0
02/11/2020
Approval date [1] 306842 0
Ethics approval number [1] 306842 0

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

Contacts
Principal investigator
Name 105198 0
Dr Helen Keen
Address 105198 0
Fiona Stanley Hospital
11 Robin Warren Drive
Murdoch, Western Australia
6150
Country 105198 0
Australia
Phone 105198 0
+61861522222
Fax 105198 0
Email 105198 0
helen.keen@uwa.edu.au
Contact person for public queries
Name 105199 0
Kylan Pathmanathan
Address 105199 0
Fiona Stanley Hospital
11 Robin Warren Drive
Murdoch, Western Australia
6150
Country 105199 0
Australia
Phone 105199 0
+61 8 61522222
Fax 105199 0
Email 105199 0
kylan.pathmanathan@health.wa.gov.au
Contact person for scientific queries
Name 105200 0
Helen Keen
Address 105200 0
Fiona Stanley Hospital
11 Robin Warren Drive
Murdoch, Western Australia
6150
Country 105200 0
Australia
Phone 105200 0
+61861522222
Fax 105200 0
Email 105200 0
helen.keen@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics have not agreed to this.


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.