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| Sponsor: | The George Institute |
|---|---|
| Collaborators: |
Institut De Recherche International Servier University of Sydney National Health and Medical Research Council, Australia |
| Information provided by: | The George Institute |
| ClinicalTrials.gov Identifier: | NCT00145925 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes Mellitus, Type 2 |
Drug: Perindopril-indapamide Drug: Gliclazide MR-based glucose lowering |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double-Blind Primary Purpose: Prevention |
| Official Title: | ADVANCE - Action in Diabetes and Vascular Disease: Preterax and Diamicron - MR Controlled Evaluation |
| Enrollment: | 11140 |
| Study Start Date: | June 2001 |
| Study Completion Date: | March 2008 |
| Primary Completion Date: | March 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Blood pressure
Perindopril indapamide vs placebo
|
Drug: Perindopril-indapamide |
|
Glucose control
Standard versus intensive glucose control
|
Drug: Gliclazide MR-based glucose lowering |
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.
Eligibility| Ages Eligible for Study: | 55 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A substantially elevated risk of cardiovascular disease, indicated by:
Exclusion Criteria:
Other potential reasons for ineligibility include:
Final decisions about eligibility were made at the discretion of the study investigator and the potential study participant, in the light of any requirements or guidance from local ethics committees and other regulatory bodies.
Contacts and Locations| Australia, Victoria | |
| The University of Melbourne | |
| Melbourne, Victoria, Australia, 3010 | |
| Canada, Quebec | |
| University of Montreal | |
| Montreal, Quebec, Canada, H26 1X2 | |
| China, Beijing | |
| Cardiovascular Institute & Fu Wai Hospital | |
| Xicheng District, Beijing, China, 100037 | |
| Netherlands | |
| The Julius Center for Health Sciences and Primary Care | |
| Utrecht, Netherlands, 3508 BA | |
| United Kingdom | |
| Imperial College School of Medicine | |
| London, United Kingdom, W2 1PG | |
| Principal Investigator: | John Chalmers, MB BS PhD | The George Institute |
| Principal Investigator: | Stephen W MacMahon, BSc PhD MPH | The George Institute |
More Information
| ClinicalTrials.gov Identifier: | NCT00145925 History of Changes |
| Other Study ID Numbers: | ADVANCE |
| Study First Received: | September 2, 2005 |
| Last Updated: | September 16, 2008 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration; New Zealand: Health Research Council; Philippines: Department of Health; Malaysia: Ministry of Health; India: Ministry of Health; China: State Food and Drug Administration; Canada: Health Canada; United Kingdom: Medicines and Healthcare Products Regulatory Agency; Ireland: Irish Medicines Board; Lithuania: State Medicine Control Agency - Ministry of Health; Russia: Pharmacological Committee, Ministry of Health; Netherlands: Medical Ethics Review Committee (METC); France: Afssaps - French Health Products Safety Agency; Italy: Ministry of Health; Poland: Ministry of Health; Czech Republic: State Institute for Drug Control; Slovakia: State Institute for Drug Control; Germany: Ethics Commission; Hungary: National Institute of Pharmacy; Estonia: The State Agency of Medicine |
|
Diabetes Mellitus, Type 2 Blood Pressure Stroke MI |
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Vascular Diseases Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Cardiovascular Diseases Gliclazide Indapamide Indapamide, perindopril drug combination Perindopril Hypoglycemic Agents |
Physiological Effects of Drugs Pharmacologic Actions Diuretics Natriuretic Agents Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |