Study rationale and design of ADVANCE: action in diabetes and vascular disease--preterax and diamicron MR controlled evaluation.
OBJECTIVE
Patients with Type II (non-insulin-dependent) diabetes mellitus are at increased risk of macrovascular and microvascular disease, both of which are reduced by controlling raised blood pressure in hypertensive patients. Intensive glycaemic control has also been shown to reduce microvascular 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 with a sulphonylurea-based regimen in high-risk patients with Type II diabetes (both hypertensive and non-hypertensive) reduces the incidence of macrovascular and microvascular disease.


METHODS
The study is a 2 x 2 factorial randomised controlled trial that will include 10000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomised to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regimen or usual guidelines-based therapy. Primary outcomes are, first, the composite of nonfatal stroke, non-fatal myocardial infarction or cardiovascular death and, second, the composite of new or worsening nephropathy or diabetic eye disease. The scheduled average duration of treatment and follow-up is 4.5 years. The study will be conducted in approximately 200 centres in Australasia, Asia, Europe and North America.


CONCLUSIONS
ADVANCE is designed to provide reliable evidence on the balance of benefits and risks conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.
Institute for International Health, University of Sydney, NSW, Australia.
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004232:Diuretics / Q000627:therapeutic use*; D005907:Gliclazide / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007190:Indapamide / Q000627:therapeutic use; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020913:Perindopril / Q000627:therapeutic use; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D007004:Hypoglycemic Agents; D010919:Placebos; D013453:Sulfonylurea Compounds; D007190:Indapamide; D005907:Gliclazide; D020913:Perindopril