Vol 3, No 1 (2002): Practical Diabetology
Other materials agreed with the Editors
Published online: 2001-12-06
Study rationale and design of ADVANCE: action in diabetes and vascular disease-preterax and diamicron MR controlled evaluation
Diabetologia Praktyczna 2002;3(1):25-30.
Abstract
INTRODUCTION. 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 glycaemia 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.
MATERIAL AND METHODS. The study is a 2 x 2 factorial randomized controlled trial that will include 10 000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomized to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regiment or usual guidelines-based therapy. Primary outcomes are, first, the composite of non-fatal 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.
CONCLUSION. ADVANCE is designed to provide reliable evidence on the balance of benefits and risk conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.
MATERIAL AND METHODS. The study is a 2 x 2 factorial randomized controlled trial that will include 10 000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomized to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regiment or usual guidelines-based therapy. Primary outcomes are, first, the composite of non-fatal 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.
CONCLUSION. ADVANCE is designed to provide reliable evidence on the balance of benefits and risk conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.
Keywords: diabetes mellitusblood pressureblood glucosecardiovascular diseasediabetic nephropathydiabetic retinopathycontrolled clinical trial