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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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

coronary artery disease

acute coronary syndrome

stable coronary artery disease

Condition category

Condition code

Cardiovascular

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]

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]

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]

At the time of percutaneous coronary intervention (PCI).

Primary outcome [2]

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]

At the time of PCI

Secondary outcome [1]

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]

At the time of PCI.

Secondary outcome [2]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

The Heart Research Institute

Address [1]

7 Eliza St Newtown NSW 2042
A/Prof Sanjay Patel's group.

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

RPAH Human Research and Ethics Committee

Ethics committee address [1]

Research Ethics and Governance Office (REGO)
Suite 210A, Level 2,
RPAH Medical Centre
100 Carillon Ave
NEWTOWN NSW 2042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/10/2019

Approval date [1]

20/11/2019

Ethics approval number [1]

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

A/Prof Sanjay Patel

Address

Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.

Country

Australia

Phone

+61 02 9515 7615

Fax

Sanjay.Patel2@health.nsw.gov.au

Contact person for public queries

Name

Kaivan Vaidya

Address

Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.

Country

Australia

Phone

+61 421180537

Fax

kaivan.vaidya@gmail.com

Contact person for scientific queries

Name

Kaivan Vaidya

Address

Dept of Cardiology, Royal Prince Alfred Hospital.
Camperdown NSW 2050.

Country

Australia

Phone

+61 421180537

Fax

kaivan.vaidya@gmail.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
4510	Ethical approval					378294-(Uploaded-03-09-2019-15-48-55)-Study-related document.pdf

Results publications and other study-related documents

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No additional documents have been identified.

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