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.

Official Title

ADVANCE – Action in Diabetes and Vascular Disease: Preterax and Diamicron – MR Controlled Evaluation

Conditions

Diabetes Mellitus, Type 2

Study Type

Interventional

Study Design

Prevention, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study

Further Details

Primary Outcome Measures:

  • Composite of non-fatal stroke, non-fatal myocardial infarction or death from any cardiovascular cause [Time Frame: July 2001 – December 2007]
  • Composite of new or substantially worsening nephropathy or microvascular eye disease. [Time Frame: July 2001 – December 2007]

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. [Time Frame: July 2001 – December 2007]

Study Start

June 2001; Study completion: December 2007

Eligibility & Criteria

  • Ages Eligible for Study: 55 Years and above
  • Genders Eligible for Study: Both

Inclusion Criteria:

  1. A diagnosis of type 2 diabetes mellitus first made at age 30 years or older
  2. Age 55 years or older at entry
  3. Ability to provide informed consent
  4. 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:

  1. A definite contradication to treatment with an ACE inhibitor or a thiazide-like diuretic
  2. 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
  3. A definite and specific indication for treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
  4. A definite contra-indication to treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
  5. A definite indication for long-term full-dose or bed-time insulin therapy
  6. 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.

Total Enrolment

11140

Contact Details

The University of Melbourne, Melbourne, Victoria, 3010, Australia

Published Results: