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Trial registered on ANZCTR


Registration number
ACTRN12619001449123
Ethics application status
Approved
Date submitted
3/09/2019
Date registered
18/10/2019
Date last updated
3/06/2021
Date data sharing statement initially provided
18/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of Inflammatory mediator release, microvascular resistance, and plaque morphology after percutaneous coronary intervention in patients treated with colchicine.
Scientific title
Assessment of Inflammatory mediator release, microvascular resistance, and plaque morphology after percutaneous coronary intervention in patients treated with colchicine.
Secondary ID [1] 299169 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
coronary artery disease 314251 0
acute coronary syndrome 314255 0
stable coronary artery disease 314423 0
Condition category
Condition code
Cardiovascular 312610 312610 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be prospectively recruited into this study, with approximately half with stable coronary disease and half with an acute coronary syndrome (ACS). In the ACS cohort, patients will be allocated in an alternating but non-randomised fashion to pre-procedural oral colchicine (1 mg then 0.5 mg one hour later) or no additional therapy. The intervention will be charted and delivered by study investigators, either on the ward or the cardiac day stay unit. In cardiac catheterisation laboratory, we will isolate peripheral and coronary sinus blood inflammatory cytokines, microparticles and platelets from patients. We will also correlate microparticle release and platelet adhesiveness in ACS after stenting with plaque morphology and microvascular dysfunction, by:
A. Measuring the IMR with a pressure wire in the coronary artery.
B. Imaging of the atherosclerotic plaque with intracoronary imaging technology - optical coherence tomography (OCT)
In the stable cohort, we will collect peripheral and coronary sinus blood samples and perform OCT and IMR analysis but there will be no intervention arm, similar to the control group in the ACS cohort.
Intervention code [1] 315464 0
Treatment: Drugs
Comparator / control treatment
The control group will not receive any additional treatment beyond optimal guideline-directed medical therapy.
Control group
Active

Outcomes
Primary outcome [1] 321265 0
To measure levels of neutrophil-derived inflammatory mediators (myeloperoxidase, human neutrophil elastase, neutrophil extracellular traps) and microparticles in both stable and ACS (colchicine-treated vs untreated) patients, and evaluate differences. This is an exploratory composite primary outcome. Blood samples will be collected from the coronary sinus, and will be either frozen and stored at -80oC for later analysis (approximately 100 mls) or analysed fresh in the case of platelet function studies or other biochemistry (approximately 36 mls).
Timepoint [1] 321265 0
At the time of percutaneous coronary intervention (PCI).
Primary outcome [2] 321390 0
To measure markers of platelet adhesiveness (thiol isomerases) in both stable and ACS (colchicine-treated vs untreated) patients, and evaluate differences. Blood samples will be collected from the coronary sinus, and will be either frozen and stored at -80oC for later analysis (approximately 100 mls) or analysed fresh in the case of platelet function studies or other biochemistry (approximately 36 mls).
Timepoint [2] 321390 0
At the time of PCI
Secondary outcome [1] 374483 0
Index of microvascular resistance (IMR) in all patients, as assessed by pressure wire evaluation and administration of intracoronary adenosine to induce maximal hyperaemia.
Timepoint [1] 374483 0
At the time of PCI.
Secondary outcome [2] 374485 0
Optical coherence tomography (OCT) to image the coronary plaque and assess plaque morphology, thickness, and high-risk features such as the presence of an inflammatory cell infiltrate
Timepoint [2] 374485 0
At the time of PCI

Eligibility
Key inclusion criteria
Inclusion Criteria: Patients (>21yrs) with a clinical need for cardiac catheterisation at Royal
Prince Alfred Hospital will be invited to participate in the study.
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: Patients with greater than 50% stenosis in the left main coronary artery, cardiogenic shock or haemodynamic instability will be excluded from the study. Other exclusion criteria include age <21, pregnancy, those unable to make their own decisions, patients with moderate renal dysfunction (creatinine clearance <50 ml/min) or hepatic dysfunction (ALT [1.5 x upper limit of normal range); thrombocytopenia or leukopenia; pregnant or lactating women and women at risk of pregnancy. Patients already taking colchicine, those with evidence of active infection or inflammatory conditions that might be associated with markedly elevated hs-CRP levels in the blood (e.g., active rheumatoid arthritis) and those taking other anti-inflammatory therapies (e.g. corticosteroids) or strong CYP3A4 inhibitors will also be excluded.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Half of the ACS patients will be consented to be given short-term peri-procedural colchicine prior to their procedure (1 mg followed by 0.5 mg one hour later), as per our previous studies. The ACS patients will be enrolled in either the colchicine arm or the control arm in an alternating fashion, but will not be randomised as we are not adequately powered in this pilot study.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Numerical data will be presented as mean +/- SD for normally distributed data and as median with interquartile range for non-normally distributed data. Non- normally distributed data will be log- transformed before being used for comparison. Comparisons will be made using T–test and one-way repeat measure analysis of variance (ANOVA) between:
(i) Stable (Group 1) and unstable CAD (Group 2) patients
(ii) IMR pre and post intervention
(iii) OCT – plaque volume, morphology, macrophage clustering and IMR
(iv) OCT and Microparticle release
(v) IMR in ACS colchicine-treated versus controls
(vi) Microparticle release in ACS colchicine-treated versus controls.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/12/2019
Actual
25/06/2020
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
1/01/2022
Actual
Sample size
Target
25
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14711 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 27751 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 303710 0
Other Collaborative groups
Name [1] 303710 0
The Heart Research Institute
Country [1] 303710 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Heart Research Institute
Address
7 Eliza St Newtown NSW 2042
A/Prof Sanjay Patel's group.
Country
Australia
Secondary sponsor category [1] 303826 0
None
Name [1] 303826 0
Address [1] 303826 0
Country [1] 303826 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304236 0
RPAH Human Research and Ethics Committee
Ethics committee address [1] 304236 0
Research Ethics and Governance Office (REGO)
Suite 210A, Level 2,
RPAH Medical Centre
100 Carillon Ave
NEWTOWN NSW 2042
Ethics committee country [1] 304236 0
Australia
Date submitted for ethics approval [1] 304236 0
24/10/2019
Approval date [1] 304236 0
20/11/2019
Ethics approval number [1] 304236 0
X19-0379

Summary
Brief summary
This study first aims to evaluate whether there are differences between patients requiring stenting who have stable blockages in their coronary arteries versus those who present with unstable heart attacks. We hope to examine whether are difference in blood clotting (platelets in particular), release of inflammation markers (neutrophil-derived in particular), resistance to blood flow in the tiny capillaries of the heart muscle (microvascular resistance), and finally in morphology and composition of the culprit blockage or plaque as assessed by a technique named optical coherence tomography (OCT). In the unstable heart attack group in particular, we will also assess whether patients treated pre-procedurally with colchicine will demonstrate changes in these parameters compared to untreated controls. The purpose of the study is to identify whether colchicine could serve as a potential therapeutic option in these high-risk patients and improve outcomes by limiting adverse events such as further heart attack at the time of stenting (peri-procedural myocardial infarction). We hypothesise that levels of inflammation will be higher in unstable heart attack patients compared to patients with stable blockages, and that colchicine will attenuate the release of inflammatory products. We also hypothesise that in the unstable heart attack patients, there will be greater dysfunction in the microvessels of the heart and that this will correlate with inflammatory release and blood platelet adhesiveness, as well as with high-risk features of the culprit blockage/plaque as assessed by OCT.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96234 0
A/Prof Sanjay Patel
Address 96234 0
Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.
Country 96234 0
Australia
Phone 96234 0
+61 02 9515 7615
Fax 96234 0
Email 96234 0
[email protected]
Contact person for public queries
Name 96235 0
Kaivan Vaidya
Address 96235 0
Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.
Country 96235 0
Australia
Phone 96235 0
+61 421180537
Fax 96235 0
Email 96235 0
[email protected]
Contact person for scientific queries
Name 96236 0
Kaivan Vaidya
Address 96236 0
Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.
Country 96236 0
Australia
Phone 96236 0
+61 421180537
Fax 96236 0
Email 96236 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
Small pilot study with all results aiming to be published - no need to make IPD available.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4510Ethical approval    378294-(Uploaded-03-09-2019-15-48-55)-Study-related document.pdf



Results publications and other study-related documents

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