Blood Pressure and Glucose Lowering for the Prevention of Vascular Disease in High Risk Patients With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title: ADVANCE - Action in Diabetes and Vascular Disease: Preterax and Diamicron - MR Controlled Evaluation

Status Completed

Clinical Trial Summary

The purpose of this study is to provide information on the risks and benefits of routine blood pressure lowering (regardless of blood pressure level), and intensive lowering of blood glucose levels, in patients with Type 2 diabetes at high risk of cardiovascular events. The major outcomes of the study will be cardiovascular events (heart attack, stroke or dying as a result of cardiovascular disease), as well as new or worsening diabetic eye and kidney disease.

Clinical Trial Description

Patients with type 2 diabetes are at increased risks of macrovascular and microvascular disease, both of which are reduced by control of raised blood pressure in hypertensive individuals. 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 blood pressure lowering (with an ACE inhibitor-diuretic combination) and intensive glycaemic control (with a sulphonylurea-based regimen) in high-risk individuals with type 2 diabetes (including hypertensive and non-hypertensive subjects) reduces the incidence of both macrovascular and microvascular disease.

The study is a 2 x 2 factorial randomised controlled trial that includes 11,140 adults with type 2 diabetes at elevated risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible individuals were randomised to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regimen (aiming for HbA1c of 6.5% or lower) 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. These primary outcomes will be analysed jointly and separately. The average duration of treatment and follow-up is 5.5 to 6 years. The study is being conducted in 214 centres in Australasia, Asia, Europe and North America.

ADVANCE is designed to provide reliable evidence about the balance of benefits and risks conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, irrespective of initial blood pressure or glucose levels. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Vascular Diseases

• NCT number: NCT00145925
• Study type: Interventional
• Source: The George Institute
• Status: Completed
• Phase: Phase 3
• Start date: June 2001
• Completion date: March 2008