The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial

• Published in: BMJ open 2023-11, Vol.13 (11), p.e074463-e074463
• Main Authors: Boczar, Kevin Emery, Shin, Sheojung, deKemp, Robert A, Dowlatshahi, Dar, Tavoosi, Anahita, Wiefels, Christiane, Liu, Peter, Lochnan, Heather, MacPherson, Paul A, Chong, Aun Yeong, Torres, Carlos, Leung, Eugene, Tawakol, Ahmed, Ahmadi, Ali, Garrard, Linda, Lefebvre, Chantal, Kelly, Cathy, MacPhee, Poppy, Tilokee, Everad, Raggi, Paolo, Wells, George A, Beanlands, Rob
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Biomarkers; cardiovascular imaging; Cardiovascular medicine; coronary heart disease; Diabetes; Double-blind studies; Medical imaging; Mortality; myocardial infarction; stroke; Transient ischemic attack; Tumor necrosis factor-TNF
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-074463

BackgroundInflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy.ObjectiveThe primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine’s effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes.Methods and designCADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30–120 days after an ACS (ie, ST-elevation