Protocol

A Mandarin version of this overview is available

ACE is a double-blind, randomised, multi-centre, cardiovascular intervention study being undertaken by the University of Oxford Diabetes Trials Unit (DTU).  The Study has been designed by Professor Rury Holman from Oxford University, UK, Professor Hu Da Yi from People's Hospital Peking University and Professor Pan Chang Yu from the Chinese PLA General Hospital, Beijing, China.  The study will be conducted in up to 150 hospitals in mainland China and Hong Kong commencing in 2008.  Patients will be followed for a minimum of 4 years and results are expected in 2016. The participating hospitals will be managed on a day-to-day basis through the ACE Project Office in Beijing.

Study Objectives

The ACE study aims to determine whether acarbose therapy can reduce cardiovascular-related morbidity and mortality in patients with impaired glucose intolerance (IGT) who have established cardiovascular disease (CVD) or acute coronary syndrome (ACS). A secondary objective of the study is to determine if acarbose therapy can prevent or delay transition to type 2 diabetes mellitus (T2DM) in this patient population. 

Primary Endpoint

Composite endpoint defined as the time to the first occurrence after randomisation of any of:

• Cardiovascular death
• Non-fatal MI
• Non-fatal stroke

Secondary Endpoints

• Transition to type 2 diabetes confirmed by two successive diagnostic plasma glucose values (FPG ≥7.0 mmol/l and/or 2HPG ≥11.1 mmol/l)
• All cause mortality
• Composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke, hospitalisation for heart failure or hospitalisation for unstable angina. Each of the components of this composite will also be analysed individually, both as first and as total events
• Proportion of patients with evidence of non-alcoholic fatty liver disease (NAFLD) as judged by changes in ALT levels
• Proportion of patients with impaired renal function as evidenced by:
  • A reduced eGFR (< 30ml/minute/1.73 m²) estimated using the Chinese MDRD formula
  • A doubling of the baseline plasma creatinine level
  • A halving of the baseline eGRF
• Resource use, costs and cost effectiveness

Study Population

• 7,500 patients (male or female)
• Aged ≥50 years
• Confirmed CVD (i.e. history of MI, previous unstable angina, current stable angina)
• IGT diagnosed on single OGTT defined as a 2-hr plasma glucose value ≥7.8 but ≤11.1 mmol/l and FPG <7.0 mmol/l
• Stable drug therapy with no planned procedures
• No evidence of hepatic disease or renal impairment

Study Treatments

Patients will be randomised to one of the following two regimens:

• Acarbose tablets (50mg)
• Placebo to match acarbose 50mg tablet

A 'Start low, Go slow' dose titration scheme will be used. By the third week post-randomisation, patients should be fully titrated and will be required to take one tablet three times a day with meals.  CVD therapy will be optimised during the run-in period to conform with international guidelines.

Assessment Periods

Patients will attend study visits every four months post randomisation for a minimum of four years.

Statistical Analysis

Assuming:

• A 3.5% per year primary event rate
• A 20% relative reduction in primary composite event rate
• An 18 month accrual period
• Alpha of 5%,

ACE Study, Diabetes Trials Unit, OCDEM, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ
Tel: +44 (0)1865 857257     Fax: +44 (0)1865 857256     Email: ace@dtu.ox.ac.uk

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