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Trial registered on ANZCTR


Registration number
ACTRN12621000665831
Ethics application status
Approved
Date submitted
20/04/2021
Date registered
1/06/2021
Date last updated
1/11/2022
Date data sharing statement initially provided
1/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The CHARISMA trial- Colchicine and High-risk plaque Assessed by peRIcoronary adipoSe tissue inflamMAtion
Scientific title
The effect of colchicine on pericoronary adipose tissue inflammation and coronary artery plaque progression in adults with high-risk plaques: Insights from cardiac computed tomography using pericoronary adipose tissue attenuation and radiomics
Secondary ID [1] 303833 0
Nil known
Universal Trial Number (UTN)
U1111-1267-3249
Trial acronym
CHARISMA trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 321358 0
Condition category
Condition code
Cardiovascular 319139 319139 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive oral colchicine 0.5mg tablets daily for 12 month in addition to the standard medical therapy (statin +/- aspirin) for nonobstructive coronary artery disease.

Medication adherence will be assessed indirectly by pill counts. Participants will be asked to count the number of pills remain in their medication bottles during scheduled review at month 1, 3, 6, 9, and 12.
Intervention code [1] 320137 0
Treatment: Drugs
Comparator / control treatment
Participants will receive placebo (microcrystalline cellulose) tablets daily for 12 month in addition to the standard medical therapy for nonobstructive coronary artery disease.
Control group
Placebo

Outcomes
Primary outcome [1] 327021 0
Percentage change in peri-coronary adipose tissue attenuation as assessed by cardiac CT angiogram.
Timepoint [1] 327021 0
At baseline and at 12 months
Secondary outcome [1] 393477 0
Difference in radiomics parameters of peri-coronary adipose tissue assessed via CT coronary angiogram
Timepoint [1] 393477 0
At baseline and at 12 months
Secondary outcome [2] 393478 0
Differences in radiomics parameters of coronary plaques assessed via CT coronary angiogram
Timepoint [2] 393478 0
At baseline and at 12 months
Secondary outcome [3] 393479 0
Change in coronary CT minimal lumen area of the non-obstructive plaque
Timepoint [3] 393479 0
At baseline and at 12 months
Secondary outcome [4] 393480 0
Change in the size of low-attenuation plaque assessed via CT coronary angiogram
Timepoint [4] 393480 0
At baseline and at 12 months
Secondary outcome [5] 393481 0
Change in plaque spotty calcification assessed via CT coronary angiogram
Timepoint [5] 393481 0
At baseline and at 12 months
Secondary outcome [6] 393482 0
Change in plaque positive remodelling assessed via CT coronary angiogram
Timepoint [6] 393482 0
At baseline and at 12 months

Eligibility
Key inclusion criteria
1. Participants who undergo clinically indicated coronary CT angiogram (CCTA) which subsequently demonstrated one or more high-risk plaques (HRP). HRP features includes any of the following: 1) positive remodelling 2) low attenuation plaque (LAP) 3) spotty calcification or 4) ‘napkin ring’ sign.
2. Participants able to provide written informed consent before baseline angiography.
3. Male or female, aged between 18 and 80 years of age at screening.
4. Participants able to be randomised within seven days of CCTA.
5. Baseline CCTA imaging determined to be of acceptable quality.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Left main coronary disease (> 50% reduction in lumen diameter by angiographic visual estimation).
2. Heart failure (New York Heart Association (NYHA) class IV) or LVEF 35% or less.
3. Participants with known gout within the last 5 years.
4. Currently prescribed colchicine for other indication, presence of contraindications to colchicine, known prior intolerance to colchicine. Concomitant therapy with drugs that could interact with colchicine (eg strong CYP3A4).
5. Dialysis or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m².
6. Thyroid stimulating hormone (TSH) < lower limit of normal (LLN) or >1.5x upper limit of normal (ULN).
7. Active liver disease or hepatic dysfunction, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN as determined by analysis at screening.
8. Known major active infection, or major haematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction.
9. Significant haematological abnormalities on assessment of complete blood picture: Hb <100 g/L, Plt <150x103 /µL, white cell count < 3.5x103 /µL.
10. History of malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or stage 1 prostate carcinoma).
11. Female participants cannot be pregnant or breast feeding, and premenopausal participants must be willing to use at least 2 highly effective method of birth control during treatment and for an additional 12 weeks after the end of treatment.
12. Unable to give informed consent.
13. Not willing or able to attend follow up visits or follow up CCTA at 6 months.
14. Any other information that the investigator considers will limit the ability of the participant to complete all study associated procedures.

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 concealment will be performed by a computer-generated central randomisation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Minimisation using computer-generated software
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
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Intention-to-treat analysis will be the primary analysis. Descriptive statistics will be presented as percentage frequencies for categorical variables and as mean ± SD (or as median with interquartile range) for continuous variables by treatment group. Baseline characteristics between groups will be compared using Chi-squared (or Fisher’s exact) test for categorical variables and independent t-test. Continuous variables will be tested for normality and appropriate non-parametric tests will be used for variables not normally distributed. The correlation between change of PCAT attenuation and change of plaque parameters were assessed by Pearson correlation or the Spearman’s test. We will explore relationships between % change in PCAT attenuation and % change in inflammatory biomarkers in the colchicine group using a simple regression model. Multivariable analysis will be used to determine independent predictors of colchicine responsiveness. Per protocol analysis will be performed on those with treatment compliance >80% as a sensitivity analysis. Computations will be performed with IBM SPSS Statistics for Windows (version 26.0. Armonk, NY). P values of <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/11/2021
Actual
8/07/2022
Date of last participant enrolment
Anticipated
31/01/2023
Actual
Date of last data collection
Anticipated
31/01/2024
Actual
Sample size
Target
50
Accrual to date
14
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 19042 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 33589 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 308228 0
Hospital
Name [1] 308228 0
Monash Cardiovascular Research Centre, Monash Medical Centre
Country [1] 308228 0
Australia
Primary sponsor type
Hospital
Name
Monash Cardiovascular Research Centre, Monash Medical Centre
Address
246 Clayton Road, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 309022 0
None
Name [1] 309022 0
Address [1] 309022 0
Country [1] 309022 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308210 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 308210 0
Research Support Services
Level 2, i Block
Monash Medical Centre
246 Clayton Road
CLAYTON VIC 3168
Ethics committee country [1] 308210 0
Australia
Date submitted for ethics approval [1] 308210 0
20/04/2021
Approval date [1] 308210 0
02/09/2021
Ethics approval number [1] 308210 0
RES-21-0000-240A

Summary
Brief summary
The CHARISMA trial is a prospective double-blind, placebo-controlled randomised study to evaluate the effect of adding colchicine to standard medical therapy in patients who have non-obstructive but high-risk plaques in their coronary arteries as demonstrated on cardiac CT angiogram (CCTA). A total of 100 participants will be recruited over the study period. Participants will be randomised to either 1) standard medical therapy or 2) standard therapy plus colchicine 0.5mg daily for 12 months. At the end of 12 months, all participants will then undergo a repeat CCTA.

We hypothesise that the addition of colchicine to standard medical therapy will have demonstrate a reduction in markers of coronary inflammation as assessed by peri-coronary adipose tissue attenuation.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109942 0
A/Prof Dennis Thiam Leong Wong .
Address 109942 0
Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 109942 0
Australia
Phone 109942 0
+61 3 9594 4543
Fax 109942 0
Email 109942 0
dennis.wong@monash.edu
Contact person for public queries
Name 109943 0
Dr Kevin Cheng
Address 109943 0
Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 109943 0
Australia
Phone 109943 0
+61 3 95946666
Fax 109943 0
Email 109943 0
kevin.cheng@monash.edu
Contact person for scientific queries
Name 109944 0
Dr Kevin Cheng
Address 109944 0
Monash Cardiovascular Research Centre
MonashHeart, Monash Health
Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 109944 0
Australia
Phone 109944 0
+61 3 95946666
Fax 109944 0
Email 109944 0
kevin.cheng@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11217Study protocol  kevin.cheng@monash.edu
11218Informed consent form    381721-(Uploaded-20-04-2021-07-01-29)-Study-related document.pdf



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.