Aernoud Fiolet

102 Chapter 4 Participants and their doctors were advised about the need to avoid co- administration of macrolide antibiotics (azithromycin, clarithromycin, erythromycin) and to temporally cease their trial medication should they be prescribed non-study colchicine for any purpose. Follow-up Every 6 months participants are required to present in person to be resupplied with trial medication and provide feedback about the status of their health. Outcomes are recorded including admission to hospital for myocardial infarction, coronary intervention, stroke or atrial fibrillation. Participants are asked to report if they interrupted their trial medication for any reason, and the reason noted. To ensure participants do not inadvertently run out of their trial medication, they are supplied with adequate tablets for 7 months. Compliance is assessed by visual estimate of the remaining supply of trial medication returned. In addition, all participants are followed according to standard care. All correspondence related to clinical visits, any hospital admissions, investigations and reports are obtained to determine and verify the occurrence of and potential primary, secondary and tertiary outcome events. Study outcomes Primary outcome The primary outcome of the study is the composite of CV death, myocardial infarction, ischemic stroke, and ischemia-driven coronary revascularization. Secondary outcomes The secondary outcomes include (1) Myocardial infarction, (2) Ischemia-driven coronary revascularization, (3) Cardiovascular death or myocardial infarction, (4) Cardiovascular death, (5) Death from any cause, and (6) the composite of sudden cardiac death, non-fatal out of hospital cardiac arrest, acute myocardial infarction, unstable angina irrespective of revascularization, or atherosclerotic ischemic stroke (the primary outcome of the first LoDoCo trial). 30 Tertiary outcomes Three tertiary outcomes associated with a pro-inflammatory state are also being tracked, including (1) new onset or recurrence of atrial onset fibrillation or atrial flutter, 31,32 (2) new onset of diabetes, 33 and (3) deep vein thrombosis and/or pulmonary embolism 34 .