Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000585729
Ethics application status
Approved
Date submitted
31/03/2022
Date registered
20/04/2022
Date last updated
3/04/2024
Date data sharing statement initially provided
20/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of repurposing low-dose colchicine in older populations on platelet activation and inflammation (CO-OPERATE): A pilot trial.
Scientific title
The effect of repurposing low-dose colchicine in older populations on platelet activation and inflammation (CO-OPERATE): A pilot trial.
Secondary ID [1] 306805 0
Nil known
Universal Trial Number (UTN)
Trial acronym
CO-OPERATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ageing 325947 0
Condition category
Condition code
Cardiovascular 323259 323259 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral tablet of colchicine (500 mcg daily or twice daily) for four weeks post enrolment
Adherence will be monitored by drug return.
Intervention code [1] 323269 0
Treatment: Drugs
Intervention code [2] 323321 0
Prevention
Comparator / control treatment
Control: usual care (the normal medicines that the patient is taking prior to the study)
Control group
Active

Outcomes
Primary outcome [1] 330947 0
Blood sample to assess change in platelet function with stimulation (aggregometry using agonists - adenosine diphosphate (ADP), thrombin and collagen) [composite]
Timepoint [1] 330947 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [1] 408209 0
Blood samples assessing surface markers of platelet activation under resting conditions
Timepoint [1] 408209 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [2] 408210 0
Blood samples assessing change in coagulation markers (INR, APTT, PT)
Timepoint [2] 408210 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [3] 408211 0
Adverse effects: nausea, vomiting, abdominal pain, diarrhoea using the Common Terminology Criteria for Adverse Events (CTCAE5.0)
Timepoint [3] 408211 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [4] 408452 0
Blood samples assessing surface markers of platelet activation post stimulation with agonists
Timepoint [4] 408452 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [5] 408453 0
Blood samples assessing D-Dimer
Timepoint [5] 408453 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [6] 408455 0
Blood samples assessing inflammatory markers (CRP, IL6, IL1-beta, TNF-alpha)
Timepoint [6] 408455 0
Baseline, 4 weeks post intervention commencement
Secondary outcome [7] 408456 0
Adherence (pill count)
Timepoint [7] 408456 0
4 weeks post commencement of intervention

Eligibility
Key inclusion criteria
• People aged >= 70yrs not on medication or comorbidities affecting platelet function.
• Able to provide signed informed consent.
• Willingness to participate and comply with the study requirements.
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Medications and comorbidities affecting platelet function: on antiplatelet agent, anticoagulation, non steroid anti-inflammatory drugs (within 7 days), fish oil supplements (within 7 days), acute myocardial infarction, past cardiovascular disease, pulmonary embolism, active cancer, active sepsis or bleeding/clotting disorders.
• Definite indication for colchicine, such as acute gout or acute pericarditis
• Contraindication to colchicine, including:
• Hypersensitivity
• Currently taking or might need during the trial, a concomitant treatment which is contraindicated with colchicine: cyclosporin, strong CYP3A4 inhibitors, phenylbutazone, immunosuppressants and anti-neoplastic agents.
• Current/history of inflammatory bowel disease, chronic diarrhea, blood dyscrasias or eGFR<15mL/min/1.73m2.
• Current surgical or medical conditions that might significantly alter the absorption, distribution, metabolism, or excretion of trial drugs such as prior major gastrointestinal tract surgery (e.g. gastrectomy, lap band, or bowel resection)
• History of alcohol or drug abuse within 12 months.
• Resident of aged care facility or significant cognitive impairment precluding consent

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment by REDCap database
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) and administered by REDCap.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculation:
In this pilot trial, we will aim for a total of 60 patients (twenty patients in each group).

Analysis plan:
Analyses will be performed on an intention-to-treat basis. Baseline characteristics will be compared using descriptive analyses. Continuous variables will be expressed as mean ± standard deviation and categorical variables as absolute counts with percentages. Differences between continuous and categorical variables will be analysed by using the Student’s t-test and the chi-2 test. We will investigate the possible effects of baseline effect modifiers or confounders including frailty using logistic regression analysis. Statistical significance will be set at p<0.05. All analyses will be performed SPSS V15, or higher. A prespecified interim analysis will be performed post recruitment of 6-30 patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/04/2022
Actual
25/04/2022
Date of last participant enrolment
Anticipated
27/11/2025
Actual
Date of last data collection
Anticipated
27/12/2025
Actual
Sample size
Target
60
Accrual to date
23
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 22094 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 37217 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 311142 0
Government body
Name [1] 311142 0
Australian Health Research Alliance Translation Network, Australian Government Department of Health,
Country [1] 311142 0
Australia
Primary sponsor type
Hospital
Name
Concord Hospital Cardiology Department
Address
Concord Hospital Cardiology Department, Hospital Rd, Concord, NSW 2139
Country
Australia
Secondary sponsor category [1] 312494 0
None
Name [1] 312494 0
Address [1] 312494 0
Country [1] 312494 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310667 0
Sydney Local Health District Human Research Ethics Committee - Concord Repatriation General Hospital
Ethics committee address [1] 310667 0
Concord Hospital, Hospital Rd, Concord, NSW, 2139
Ethics committee country [1] 310667 0
Australia
Date submitted for ethics approval [1] 310667 0
05/10/2021
Approval date [1] 310667 0
16/12/2021
Ethics approval number [1] 310667 0
2021/ETH11709

Summary
Brief summary
While the ability to effectively prevent cardiovascular disease (CVD) in the elderly is imperative, there are few primary prevention therapies. The gout medicine colchicine inhibits the critical pathways of inflammation and platelet activation involved in atherothrombosis, but does not increase bleeding. Colchicine has a broad anti-inflammatory effect. Benefits of long-term low-dose colchicine have been confirmed in people with established coronary artery disease, with a substantial 31% (95%CI 22-40%) reduction in cardiovascular events. We have demonstrated that older people have a distinctive platelet phenotype of increased basal activation, hyperreactivity to adenosine diphosphate and thrombin resistance, correlating with elevated inflammation. Thrombin generation associated with systemic inflammation was identified as a possible novel target to prevent CVD in the elderly. A small pilot trial will be used to assess the effectiveness and safety of colchicine compared to usual care in inhibiting platelet activation and inflammation in elderly patients without cardiovascular disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118458 0
Dr Sonali Gnanenthiran
Address 118458 0
3W, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW, 2139
Country 118458 0
Australia
Phone 118458 0
+61297677282
Fax 118458 0
Email 118458 0
sgnanenthiran@georgeinstitute.org.au
Contact person for public queries
Name 118459 0
Dr Sonali Gnanenthiran
Address 118459 0
3W, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW, 2139
Country 118459 0
Australia
Phone 118459 0
+61297677282
Fax 118459 0
Email 118459 0
sgnanenthiran@georgeinstitute.org.au
Contact person for scientific queries
Name 118460 0
Dr Sonali Gnanenthiran
Address 118460 0
3W, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW, 2139
Country 118460 0
Australia
Phone 118460 0
+61297677282
Fax 118460 0
Email 118460 0
sgnanenthiran@georgeinstitute.org.au

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?

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.