COLchicine and Non-enteric Coated Aspirin in the Cardiovascular Outcomes Trial of Patients With Type 2 Diabetes

Exclusion Criteria24

• Any prior history of myocardial infarction, angina, coronary revascularization, coronary stenosis \>30%, stroke, transient ischemic attack, or known heart failure
• Known chronic renal insufficiency defined as an estimated glomerular filtration rate (eGFR), using the MDRD equation, of \< 35 mL/min/1.73m2
• History of cancer or lymphoproliferative disease within the last 3 years other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or low-grade prostate cancer
• Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or chronic diarrhea
• Peptic ulcer diagnosed within the last 24 months or previous gastro-intestinal bleeding, except for mild hemorrhoidal bleeding more than 5 years ago which is permitted (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
• Pre-existent progressive neuromuscular disease or known CPK level \> 3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing
• Any of the following known parameters as measured within the past 90 days, and determined to be non-transient through repeat testing:
• hemoglobin \< 100 g/L
• \. white blood cell count \< 3.0 X 10⁹/L
• platelet count \<110 X 10⁹/L
• ALT \> 3 times the upper limit of normal (ULN)
• total bilirubin \> 2 times ULN (unless due to Gilbert syndrome, which is allowed)
• History of cirrhosis, chronic active hepatitis or severe hepatic disease
• Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study or for 6 months after the last dose of study medication
• History of clinically significant drug or alcohol abuse in the last year
• Patient is currently using or plans to begin chronic systemic steroid therapy (oral or intravenous) during the study (topical or inhaled steroids are allowed, as well as replacement corticosteroids for adrenal insufficiency)
• Current chronic treatment with aspirin or another antiplatelet agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
• Chronic treatment with an anticoagulant agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
• Current use of colchicine for other indications (mainly chronic indications consisting of Familial Mediterranean Fever or gout); there is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment
• History of an allergic reaction or significant sensitivity to colchicine
• History of an allergic reaction or significant sensitivity to aspirin (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
• Chronic treatment with an anti-inflammatory agent (for example, anti-TNF-alpha or nonsteroidal anti-inflammatory drug (NSAID))
• Use of an investigational chemical agent less than 30 days or 5 half-lives prior to the screening visit (whichever is longer)
• Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.