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

Primary Purpose

Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Perindopril-indapamide
Gliclazide MR-based glucose lowering
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Type 2 focused on measuring Diabetes Mellitus, Type 2, Blood Pressure, Stroke, MI

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A diagnosis of type 2 diabetes mellitus first made at age 30 years or older Age 55 years or older at entry Ability to provide informed consent A substantially elevated risk of cardiovascular disease, indicated by: A history of major macrovascular disease defined as any one of: stroke, myocardial infarction, hospital admission for transient ischaemic attack, hospital admission for unstable angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty (with or without stenting), peripheral revascularisation (angioplasty or surgery) or amputation secondary to vascular disease or A history of major microvascular disease defined as any one of nephropathy (albumin:creatinine ratio >300ug/mg), retinal photocoagulation therapy, proliferative retinopathy (new blood vessels on the disc or elsewhere, vitreous haemorrhage, pre-retinal haemorrhage, or fibrous proliferations on the disc or elsewhere), macular oedema (retinal thickening within one disc diameter of the macular centre) or blindness in either eye (corrected visual acuity 6/60 or worse, persisting for three months or more) not known to be due to non-diabetic causes or A first diagnosis of type 2 diabetes made 10 or more years prior to entry or Another major risk factor for vascular disease defined as any one of: current daily cigarette smoking, total cholesterol greater than 6.0 mmol/l (with or without cholesterol lowering treatment), HDL cholesterol <1.0 mmol/l, microalbuminuria (albumin:creatinine ratio 30-300ug/mg) or Age 65 years or over Exclusion Criteria: A definite contraindication to treatment with an ACE inhibitor or a thiazide-like diuretic A specific indication for treatment with an ACE inhibitor other than perindopril 2-4 mg daily (see also section 5.2.3) or a thiazide-like diuretic A definite and specific indication for treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less A definite contra-indication to treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less A definite indication for long-term full-dose or bed-time insulin therapy Participation in a trial within the month prior to the Registration Visit or current participation in another trial Other potential reasons for ineligibility include: High probability of non-adherence to study treatment or follow-up Current clinical instability (e.g. a major cerebral or coronary event or sight-threatening retinopathy or macular oedema within the previous few weeks) Life threatening non-vascular disease other than diabetes and its complications Moderate or severe dementia Major disability that is likely to prevent regular attendance at study clinics 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.

Sites / Locations

  • The University of Melbourne
  • University of Montreal
  • Cardiovascular Institute & Fu Wai Hospital
  • The Julius Center for Health Sciences and Primary Care
  • Imperial College School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Other

Arm Label

Blood pressure

Glucose control

Arm Description

Perindopril indapamide vs placebo

Standard versus intensive glucose control

Outcomes

Primary Outcome Measures

Composite of non-fatal stroke, non-fatal myocardial infarction or death from any cardiovascular cause
Composite of new or substantially worsening nephropathy or microvascular eye disease.

Secondary Outcome Measures

Includes cerebrovascular disease, coronary heart disease, heart failure, peripheral vascular disease, cardiovascular and all-cause mortality, microalbuminuria, visual deterioration, new or worsening nephropathy, cognitive function, and dementia.

Full Information

First Posted
September 2, 2005
Last Updated
September 16, 2008
Sponsor
The George Institute
Collaborators
Institut de Recherches Internationales Servier, University of Sydney, National Health and Medical Research Council, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT00145925
Brief Title
Blood Pressure and Glucose Lowering for the Prevention of Vascular Disease in High Risk Patients With Type 2 Diabetes
Official Title
ADVANCE - Action in Diabetes and Vascular Disease: Preterax and Diamicron - MR Controlled Evaluation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2008
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
The George Institute
Collaborators
Institut de Recherches Internationales Servier, University of Sydney, National Health and Medical Research Council, Australia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Diabetes Mellitus, Type 2, Blood Pressure, Stroke, MI

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
Double
Allocation
Randomized
Enrollment
11140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blood pressure
Arm Type
Placebo Comparator
Arm Description
Perindopril indapamide vs placebo
Arm Title
Glucose control
Arm Type
Other
Arm Description
Standard versus intensive glucose control
Intervention Type
Drug
Intervention Name(s)
Perindopril-indapamide
Intervention Type
Drug
Intervention Name(s)
Gliclazide MR-based glucose lowering
Primary Outcome Measure Information:
Title
Composite of non-fatal stroke, non-fatal myocardial infarction or death from any cardiovascular cause
Time Frame
July 2001 - December 2007
Title
Composite of new or substantially worsening nephropathy or microvascular eye disease.
Time Frame
July 2001 - December 2007
Secondary Outcome Measure Information:
Title
Includes cerebrovascular disease, coronary heart disease, heart failure, peripheral vascular disease, cardiovascular and all-cause mortality, microalbuminuria, visual deterioration, new or worsening nephropathy, cognitive function, and dementia.
Time Frame
July 2001 - December 2007

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A diagnosis of type 2 diabetes mellitus first made at age 30 years or older Age 55 years or older at entry Ability to provide informed consent A substantially elevated risk of cardiovascular disease, indicated by: A history of major macrovascular disease defined as any one of: stroke, myocardial infarction, hospital admission for transient ischaemic attack, hospital admission for unstable angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty (with or without stenting), peripheral revascularisation (angioplasty or surgery) or amputation secondary to vascular disease or A history of major microvascular disease defined as any one of nephropathy (albumin:creatinine ratio >300ug/mg), retinal photocoagulation therapy, proliferative retinopathy (new blood vessels on the disc or elsewhere, vitreous haemorrhage, pre-retinal haemorrhage, or fibrous proliferations on the disc or elsewhere), macular oedema (retinal thickening within one disc diameter of the macular centre) or blindness in either eye (corrected visual acuity 6/60 or worse, persisting for three months or more) not known to be due to non-diabetic causes or A first diagnosis of type 2 diabetes made 10 or more years prior to entry or Another major risk factor for vascular disease defined as any one of: current daily cigarette smoking, total cholesterol greater than 6.0 mmol/l (with or without cholesterol lowering treatment), HDL cholesterol <1.0 mmol/l, microalbuminuria (albumin:creatinine ratio 30-300ug/mg) or Age 65 years or over Exclusion Criteria: A definite contraindication to treatment with an ACE inhibitor or a thiazide-like diuretic A specific indication for treatment with an ACE inhibitor other than perindopril 2-4 mg daily (see also section 5.2.3) or a thiazide-like diuretic A definite and specific indication for treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less A definite contra-indication to treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less A definite indication for long-term full-dose or bed-time insulin therapy Participation in a trial within the month prior to the Registration Visit or current participation in another trial Other potential reasons for ineligibility include: High probability of non-adherence to study treatment or follow-up Current clinical instability (e.g. a major cerebral or coronary event or sight-threatening retinopathy or macular oedema within the previous few weeks) Life threatening non-vascular disease other than diabetes and its complications Moderate or severe dementia Major disability that is likely to prevent regular attendance at study clinics 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Chalmers, MB BS PhD
Organizational Affiliation
The George Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen W MacMahon, BSc PhD MPH
Organizational Affiliation
The George Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Melbourne
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3010
Country
Australia
Facility Name
University of Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H26 1X2
Country
Canada
Facility Name
Cardiovascular Institute & Fu Wai Hospital
City
Xicheng District
State/Province
Beijing
ZIP/Postal Code
100037
Country
China
Facility Name
The Julius Center for Health Sciences and Primary Care
City
Utrecht
ZIP/Postal Code
3508 BA
Country
Netherlands
Facility Name
Imperial College School of Medicine
City
London
ZIP/Postal Code
W2 1PG
Country
United Kingdom

12. IPD Sharing Statement

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PubMed Identifier
11848259
Citation
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http://www.thegeorgeinstitute.org/
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Blood Pressure and Glucose Lowering for the Prevention of Vascular Disease in High Risk Patients With Type 2 Diabetes

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