Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001005145
Ethics application status
Approved
Date submitted
9/07/2019
Date registered
15/07/2019
Date last updated
24/07/2019
Date data sharing statement initially provided
15/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of colchicine on neutrophils in patients presenting with an acute coronary syndrome (ACS)
Scientific title
The effect of colchicine on neutrophils in patients presenting with an acute coronary syndrome (ACS)
Secondary ID [1] 298703 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 313501 0
Acute coronary syndrome 313502 0
Condition category
Condition code
Cardiovascular 311929 311929 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1.5 mg colchicine will be administered orally in two doses – 1 mg followed by 0.5 mg one hour later.

Patients presenting with an acute coronary syndrome or stable angina will be recruited shortly after admission. Written informed consent will be obtained from all study participants. Prior to randomisation a peripheral venous blood sample (20 mL) will be collected. Patients will then be randomised to receive either colchicine (as above) plus standard medical care or standard medical care alone. 24-hours post intervention a further 20 mL peripheral venous blood sample will be collected.
Intervention code [1] 314893 0
Treatment: Drugs
Comparator / control treatment
Participants in the control cohort will receive standard medical care without colchicine.
Control group
Active

Outcomes
Primary outcome [1] 320594 0
Change in reactivity of isolated neutrophils as measured by Sytox green NETosis assay previously described by Khan & Palaniyar (2017).
Timepoint [1] 320594 0
Baseline and 24-hours post intervention
Secondary outcome [1] 372151 0
Change in myeloperoxidase concentration in isolated neutrophils. This will be analysed using enzyme-linked immunosorbent assay.
Timepoint [1] 372151 0
Baseline and 24-hours post intervention
Secondary outcome [2] 372152 0
Presence or absence of low-density neutrophils, as previously described by Sagiv, Voels & Granot (2016).
Timepoint [2] 372152 0
Baseline and 24-hours post intervention
Secondary outcome [3] 372154 0
Difference in neutrophil activation between patients with stable coronary artery disease and those presenting with an acute coronary syndrome, as measured by by Sytox green NETosis assay previously described by Khan & Palaniyar (2017).
Timepoint [3] 372154 0
Baseline and 24-hours post intervention

Eligibility
Key inclusion criteria
Age >= 18 years
ACS patients < 48 hours post presentation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Colchicine treatment for another cause
Severe liver disease
Renal insufficiency with creatinine clearance < 45 ml/min
Calcineurin inhibitor treatment
Hypersensitivity to colchicine
Haematological malignancy or antineoplastic therapy
Thrombocytopenia or leukopenia
Pregnancy, lactating women or women at risk of pregnancy
Strong CYP3A4 inhibitors
Chronic inflammatory bowel disease

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 achieved by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised using permuted blocks; stratified by presentation (ACS or Stable CAD)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on an estimated 25% reduction in the extent of neutrophil activity with colchicine treatment and with a type I error rate of 0.05 and power of 80% the sample size required is 40 (20 participants per group). This calculation is based on a recent publication with a population standard deviation of 8%.

Continuous outcomes will be assessed for normality and analysed using the appropriate parametric (t-test or ANOVA) or non-parametric (Mann Whitney) tests. Categorical variables will be assessed for independence using the Chi-Square test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/07/2019
Actual
Date of last participant enrolment
Anticipated
30/09/2019
Actual
Date of last data collection
Anticipated
4/10/2019
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14124 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 26929 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 303171 0
Charities/Societies/Foundations
Name [1] 303171 0
Perpetual IMPACT Philanthropy
Country [1] 303171 0
Australia
Primary sponsor type
Individual
Name
A/Prof Sanjay Patel
Address
Heart Research Institute
7 Eliza St, Newtown
NSW 2050
Country
Australia
Secondary sponsor category [1] 303178 0
None
Name [1] 303178 0
Address [1] 303178 0
Country [1] 303178 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303733 0
Sydney Local Health District (RPAH Zone) Human Research Ethics Committee
Ethics committee address [1] 303733 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
RPAH Medical Centre
Suite 210A, 100 Carillon Ave
Newtown NSW 2042
Ethics committee country [1] 303733 0
Australia
Date submitted for ethics approval [1] 303733 0
Approval date [1] 303733 0
14/02/2018
Ethics approval number [1] 303733 0
X180004

Summary
Brief summary
Inflammation is central to the development and progression of atherosclerosis. Neutrophils are the most abundant immune cell in circulation and contribute to atherosclerosis-associated inflammation.

Colchicine is an anti-inflammatory agent currently approved for the treatment of gout, familial Mediterranean fever and acute/recurrent pericarditis. There is mounting evidence that indicates colchicine is effective at reducing ACS recurrence rates by inhibiting specific inflammatory pathways. An anti-inflammatory effect of colchicine on neutrophils has been noted in patients with vasculitis, although this has not been examined in those with coronary artery disease. Colchicine use has been proven to be safe, well tolerated and is inexpensive and readily available.

The aim of this study is to assess the acute effect of colchicine (1.5 mg orally) on neutrophil function in patients with coronary artery disease. We hypothesis that colchicine will inhibit neutrophil hyper-reactivity seen in these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94606 0
Mr Bradley Tucker
Address 94606 0
Heart Research Institute
7 Eliza St
Newtown, NSW, 2042
Country 94606 0
Australia
Phone 94606 0
+61 2 8208 8900
Fax 94606 0
+61 2 9517 1552
Email 94606 0
[email protected]
Contact person for public queries
Name 94607 0
Mr Bradley Tucker
Address 94607 0
Heart Research Institute
7 Eliza St
Newtown, NSW, 2042
Country 94607 0
Australia
Phone 94607 0
+61 2 8208 8900
Fax 94607 0
+61 2 9517 1552
Email 94607 0
[email protected]
Contact person for scientific queries
Name 94608 0
Mr Bradley Tucker
Address 94608 0
Heart Research Institute
7 Eliza St
Newtown, NSW, 2042
Country 94608 0
Australia
Phone 94608 0
+61 2 8208 8900
Fax 94608 0
+61 2 9517 1552
Email 94608 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


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.