Etude ADVANCE: Objectifs, protocole et état actuel

Rationale: Patients with type 2 diabetes mellitus have markedly increased risks of developing vascular diseases. These risks are reduced by lowering blood pressure in hypertensive individuals. However, the association between blood pressure and vascular risk appears continuous, with no clearly defined blood pressure level below which the risks fail to further decline. Intensive glucose lowering in these patients has also been shown to reduce microvascular disease, but effects on macrovascular disease remain uncertain. Objectives: ADVANCE (Action in Diabetes and Vascular disease; preterAx and diamicroN-MR Controlled Evaluation) will examine the hypotheses that intensive blood pressure lowering (with an angiotensin-converting enzyme [ACE] inhibitor-diuretic combination) and glucose control in high-risk hypertensive or non-hypertensive individuals with type 2 diabetes reduce the incidence of vascular diseases. The study will also provide an opportunity to examine the effects of blood pressure lowering against a background of ACE inhibition among such patients. Design: This 2 x 2 factorial randomised controlled trial will recruit 10 000 adults with type 2 diabetes at elevated risk of vascular disease, from approximately 200 clinical centres in 20 countries worldwide. Eligible patients are randomised to, first, the fixed combination of perindopril 2mg/indapamide 0.625mg then perindopril 4mg/indapamide 1.25mg or matching placebo, and, second, to an intensive sulphonylurea-based glucose control regimen (target glycosylated haemoglobin [HbA_1c] ≤ 6.5%), or usual guidelines-based therapy. Any participant in whom ACE inhibition is thought to be indicated is provided with background perindopril therapy. The scheduled period of treatment and follow-up is 4.5 years. Primary outcomes are a composite of macrovascular and a composite of microvascular events. Current status: By mid-September 2002, more than 8000 patients had been recruited from 17 countries, with registrations expected to be completed by December 2002. Approximately half the participants recruited will be from Asia or from Eastern Europe. Final results are expected early in 2007.