Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001579785
Ethics application status
Approved
Date submitted
13/12/2022
Date registered
21/12/2022
Date last updated
21/12/2022
Date data sharing statement initially provided
21/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Magnetic Resonance Imaging Outcomes in Colchicine After Stroke to Prevent Event Recurrence (CASPER) study cohort: An Imaging sub-study of Colchicine After Stroke to Prevent Event Recurrence.
Scientific title
Magnetic Resonance Imaging Outcomes in the Colchicine After Stroke to Prevent Event Recurrence (MR CASPER): A randomized trial to examine the effect of long-term low-dose Colchicine on cerebrovascular disease progression and cognitive decline, incorporating Magnetic Resonance imaging and clinical assessments.
Secondary ID [1] 308582 0
None
Universal Trial Number (UTN)
Trial acronym
MR-CASPER
Linked study record
This record is a sub study to the following parent trial:
CASPER Trial: ACTRN12621001408875

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 328445 0
Atherosclerosis 328446 0
Transient Ischemic Attack 328447 0
Condition category
Condition code
Stroke 325475 325475 0 0
Ischaemic
Cardiovascular 325476 325476 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 325478 325478 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The cohort of participants randomized into the intervention arm of CASPER [ACTRN12621001408875] i.e., taking oral Colchicine 0.5mg tablet daily for median 3 years will make up the intervention arm of participants in the MR-CASPER sub-study, and will upon completing registration, run-in and randomization phases of CASPER [ACTRN12621001408875] undergo:
- Baseline Magnetic Resonance Imaging (MRI), with no contrast dye injected and a projected 30 min total scan time will be conducted by radiologist.
-Baseline cognitive assessment; Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT) and Brief Memory and Executive Test (BMET) performed by study investigators.
-Baseline mood assessment; Depression, Anxiety and Stress Scale 42 (DASS 42) performed by study investigators.
-Baseline Quality of life assessment; 36-item short form survey (SF-36) performed by study investigators.
- Follow-up MRI annually with no contrast dye injected and a projected 30 min total scan time, in line with the 12month, 24 month and 36month follow-up visits employed in the parent study CASPER [ACTRN12621001408875] conducted by radiologist.
- Follow-up cognitive (MOCA, TMT, BMET), mood (DASS 42) and quality of life (SF-36) clinical assessments are projected to take up to 45min, in line with the 12month, 24 month and 36month follow-up visits employed in the parent study CASPER [ACTRN12621001408875] conducted by study investigators.
Participant adherence to the MRI intervention will be monitored by scheduled visits attendance checklists.
Trial synergies include using concurrent assessment time-points for both studies, with assessors also shared to further reduce participant burden.
Intervention code [1] 325028 0
Diagnosis / Prognosis
Comparator / control treatment
The cohort of participants randomized into placebo arm of CASPER [ACTRN12621001408875] i.e., taking matched oral Placebo tablet daily for median 3 years will make up the control group for MR-CAPSER [ACTRN12621001408875]. The placebo tablets in CASPER [ACTRN12621001408875] are sugar pills with no active medicine.
The patients in the control arm of the MR-CAPSER study will undergo the same MRI and cognitive/mood/quality of life assessments as participants in the intervention arm of the study as outlined in the intervention description above.
Control group
Placebo

Outcomes
Primary outcome [1] 333330 0
Rate of progressive Inflammatory brain injury after Ischemic stroke compared to placebo, as measured by novel Composite CerebroVascular Disease Burden (CCVDB) outcome, which comprises presence of new ischemic lesions, progression of white matter hyperintensity and brain volume loss as detected by MRI
Timepoint [1] 333330 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [1] 416719 0
Identification of new ischemic lesions (cortical or subcortical infarcts) as detected by MRI
Timepoint [1] 416719 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [2] 416727 0
Progression of white mater hyperintensity as detected by MRI
Timepoint [2] 416727 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [3] 416728 0
Rate of stenosis, signal change indicating atherosclerotic disease as detected by MRI
Timepoint [3] 416728 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [4] 416729 0
Effect of Colchicine on quality-of-life measures after ischemic stroke compared to placebo as measured by the DASS 42 mood clinical assessment as conducted by study investigators.
Timepoint [4] 416729 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [5] 416730 0
Effect of colchicine on cognitive decline after ischemic stroke compared to placebo as measured by MOCA clinical cognitive assessments performed by study investigators.
Timepoint [5] 416730 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [6] 416910 0
Measure of brain volume loss as detected by MRI
Timepoint [6] 416910 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [7] 416961 0
Effect of Colchicine on quality-of-life measures after ischemic stroke compared to placebo as measured by the SF 36 quality-of-life clinical assessment conducted by study investigators.
Timepoint [7] 416961 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [8] 416962 0
Effect of colchicine on cognitive decline after ischemic stroke compared to placebo as measured by BMET clinical cognitive assessments performed by study investigators.
Timepoint [8] 416962 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]
Secondary outcome [9] 416963 0
Effect of colchicine on cognitive decline after ischemic stroke compared to placebo as measured by TMT clinical cognitive assessments performed by study investigators.
Timepoint [9] 416963 0
12 months, 24 months and 36 months post randomization in parent trial CASPER [ACTRN12621001408875]

Eligibility
Key inclusion criteria
Eligible participants must meet the following criteria:
1. Be enrolled in CASPER (ACTRN12621001408875) study
2. Be aged 18 years or older
3. Have recovered from an acute ischemic (non-cardioembolic) stroke without major residual disability (mRS less than or equal to 3) as per main CASPER (ACTRN12621001408875) study.
4. Have a serum measurement of high sensitivity C-Reactive Protein (hs-CRP) greater than or equal to 2 mg/L at 4-52 weeks post-event as per main CASPER (ACTRN12621001408875) study.
5. Be willing and able to comply with MR-CASPER sub-study visit schedule and nature of required assessments.
6. Provide written informed consent for the MR CASPER sub-study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants that are not eligible for CASPER (ACTRN12621001408875) study will not be included.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a randomised (1:1), placebo-controlled, double-blinded, multi-centre clinical trial of 200 participants. Allocation concealment will be as per central computerized randomization.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All the CASPER (ACTRN12621001408875) sites participating in MR-CASPER will recruit consecutive patients until completion. The randomisation in CASPER is specifically stratified by this condition, i.e., MR-CASPER can fully rely on the original randomisation for the CASPER (ACTRN12621001408875) study without undermining the integrity and validity of either study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
The study data collectors, investigators and participants will be blinded to the allocated treatment, i.e., active treatment or placebo. It is expected that the data collectors, investigators and participants will remain blinded for the entire duration of the study.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Meta-analyses of the available data suggest colchicine reduces new clinical events by ~65%. Assuming absolute risk of occurrence of the unfavorable CCVDB (Composite CerebroVascular Disease Burden) outcome will be reduced by a conservative estimate of 0.25 and using 90% power with a two-sided alpha of 0.05, we will require 81 participants in each group to detect such or a larger difference in proportions of participants with unfavourable composite CCVDB outcome at 3 years (0.7 in control arm vs 0.45 in colchicine arm). Allowing for up to 20% loss to follow-up we plan to recruit a total of 200 participants.

The primary outcome (the proportion of patients with unfavourable CCVDB outcome at 36 months) will be analysed using logistic regression including treatment group as an independent variable, and age, baseline brain volume, baseline WMH volume as covariates. The treatment effect will be reported as an adjusted odds ratio with 95% confidence interval and p-value.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/03/2023
Actual
Date of last participant enrolment
Anticipated
31/03/2024
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 23707 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 23708 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 23709 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 23710 0
John Hunter Hospital - New Lambton
Recruitment hospital [5] 23712 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 39143 0
2170 - Liverpool
Recruitment postcode(s) [2] 39144 0
2031 - Randwick
Recruitment postcode(s) [3] 39145 0
3050 - Parkville
Recruitment postcode(s) [4] 39146 0
2305 - New Lambton
Recruitment postcode(s) [5] 39148 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 312832 0
Government body
Name [1] 312832 0
National Health and Medical Research Council (NHMRC), Clinical Trial and Cohorts Grant
Country [1] 312832 0
Australia
Primary sponsor type
Government body
Name
South Western Sydney Local Health District
Address
Administration Building
Eastern Campus, Liverpool Hospital
Locked Bag 7279
LIVERPOOL BC NSW 1871
Country
Australia
Secondary sponsor category [1] 314494 0
None
Name [1] 314494 0
Address [1] 314494 0
Country [1] 314494 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312110 0
Sydney Local Health District (RPA Zone)
Ethics committee address [1] 312110 0
Ethics committee country [1] 312110 0
Australia
Date submitted for ethics approval [1] 312110 0
25/07/2022
Approval date [1] 312110 0
03/08/2022
Ethics approval number [1] 312110 0
MR CASPER - 2021/ETH11289 (Form 102494)

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

Contacts
Principal investigator
Name 123510 0
Prof Mark Parsons
Address 123510 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets,
Liverpool, NSW
2170
Country 123510 0
Australia
Phone 123510 0
+61 2 8738 6511
Fax 123510 0
Email 123510 0
[email protected]
Contact person for public queries
Name 123511 0
Mark Parsons
Address 123511 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets,
Liverpool, NSW
2170
Country 123511 0
Australia
Phone 123511 0
+61 2 8738 6511
Fax 123511 0
Email 123511 0
[email protected]
Contact person for scientific queries
Name 123512 0
Mark Parsons
Address 123512 0
Liverpool Hospital
Corner of Elizabeth and Goulburn Streets,
Liverpool, NSW
2170
Country 123512 0
Australia
Phone 123512 0
+61 2 8738 6511
Fax 123512 0
Email 123512 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Medical data pertaining to an individual will not be made public. Only aggregate summary data will be published.


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.