Study Rationale and Design of ADVANCE: Action in and vascular disease - preterax and diamicron MR evaluation

Aims/hypothesis. Patients with Type II (non-insulin dependent) diabetes mel litus are at increased risk of macrovascular and microvascular disease, bot h of which are reduced by controlling raised blood pressure in hypertensive patients. Intensive glycaemic control has also been shown to reduce microv ascular disease but the effects on macrovascular disease remain uncertain. This study will examine the hypotheses that lowering blood pressure with an ACE inhibitor-diuretic combination and intensively controlling gylcaemia w ith a sulphonylurea-based regimen in high-risk patients with Type II diabet es (both hypertensive and non-hypertensive) reduces the incidence of macrov ascular and microvascular disease. Methods. The study is a 2 x 2 factorial randomised controlled trial that will include 10 000 adults with Type II di abetes at high risk of vascular disease. Following 6 weeks on open label pe rindopril-indapamide combination, eligible patients are randomised to conti nued perindopril-indapamide or matching placebo, and to an intensive glicla zide MR-based glucose control regimen or usual guidelines-based therapy. Pr imary outcomes are, first, the composite of nonfatal stroke, non-fatal myoc ardial infarction or cardiovascular death and, second, the composite of new or worsening nephropathy or diabetic eye disease. The scheduled average du ration of treatment and follow-up is 4.5 years. The study will be conducted in approximately 200 centres in Australasia, Asia, Europe and North Americ a. Conclusion/interpretation. ADVANCE is designed to provide reliable evide nce on the balance of benefits and risks conferred by blood pressure loweri ng therapy and intensive glucose control therapy in high-risk diabetic pati ents, regardless of initial blood pressure or glucose concentrations.