Acarbose Cardiovascular Evaluation Trial

• Register: ISRCTN
• Last refreshed on: 12 February 2013
• Main ID: ISRCTN91899513
• Date of registration: 12/11/2008
• Primary sponsor: University of Oxford (UK)
• Public title: Acarbose Cardiovascular Evaluation Trial ACE
• Scientific title: The Acarbose Cardiovascular Evaluation (ACE) Trial: A 4-year, multicentre, double-blind, randomised parallel-group trial to determine whether reducing post-prandial glycaemia can reduce cardiovascular-related morbidity and mortality in patients with established coronary heart disease or acute coronary syndrome who have impaired glucose tolerance
• Date of first enrolment: Dec 15 2008
• Target sample size: 7,500
• Recruitment status: Ongoing/Recruiting
• URL: http://isrctn.org/ISRCTN91899513
• Study type: Interventional
• Study design: Phase IV multi-centre double-blind randomised controlled clinical outcome trial

Countries of recruitment

China

Contacts

• Name: Rury Holman

Key inclusion & exclusion criteria

Inclusion criteria: Current inclusion criteria as of 21/09/2011:
1. Male or female, aged 50 years or more
2. Definite CHD, defined as a, b or c below:
2.1 Previous myocardial infarction (MI) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following:
2.1.1. Typical clinical presentation
2.1.2. Confirmatory ECG changes
2.1.3. Appropriate elevation of cardiac enzymes/biomarkers
Note: Patients with stents are eligible.
2.2 Previous unstable angina (UA) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following:
2.2.1. Typical clinical presentation
2.2.2.Confirmatory ECG changes
2.2.3.Either elevation of a cardiac biomarker or a >50% stenosis in =1 major epicardial coronary artery shown on coronary angiography or CT angiography. Where stenosis is reported in a qualitative manner, the categories ?moderate? and ?severe? will be taken as equating to >50% stenosis.
2.3. Current stable angina defined as:
2.3.1. Typical clinical history with symptoms occurring within the last month, and
2.3.2. A >50% stenosis in =1 major epicardial coronary artery shown on coronary angiography or CT angiography. Where stenosis is reported in a qualitative manner, the categories ?moderate? and ?severe? will be taken as equating to >50% stenosis.
3.Impaired glucose tolerance diagnosed on a single 75g anhydrous glucose OGTT, defined as a 2-hour plasma glucose (2HPG) value =7.8 but <11.1 mmol/l and a fasting plasma glucose(FPG) <7.0 mmol/l within six months prior to enrollment.
4. Optimised cardiovascular drug therapy
5. At least 80% adherent to single blind placebo Study Medication during the run-in period
6. Provision of written informed consent

Previous inclusion criteria as of 02/03/10:

2.1. Previous myocardial infarction (MI), but not within the last 3 months, with at least two of the following:
2.2 Previous unstable angina, but not within the last 3 months, with all of the following:
2.2.1. Typical clinical presentation
2.2.2. Dynamic ECG changes
2.2.3. Either elevation of a cardiac biomarker or a >50% stenosis in =1 major epicardial coronary artery shown on coronary angiography
2.3. Current stable angina defined as:
2.3.1. Typical clinical history with symptoms occurring within the last month, and
2.3.2. A >50% stenosis in =1 major epicardial coronary artery shown on coronary angiography
3. Impaired glucose tolerance diagnosed on a single 75g anhydrous glucose OGTT, defined as a 2-hour plasma glucose (2HPG) value =7.8 but <11.1 mmol/l and a fasting plasma glucose (FPG) <7.0 mmol/l

Previous inclusion criteria at time of registration:
1. Male or female, aged 50 years or more
2. Definite CHD, defined as a, b or c below:
2.1. Previous myocardial infarction (MI), but not within the last 3 months, with all of the following:
2.1.1. Typical clinical presentation
2.1.2. Confirmatory electrocardiogram (ECG) changes
2.1.3. Appropriate elevation of cardiac enzymes/biomarkers
2.2. Previous unstable angina, but not within the last 3 months, with all of the following:
2.2.1. Typical clinical presentation
2.2.2. Dynamic ECG changes
2.2.3. Either elevation of a cardiac biomarker or a >50% stenosis in >=1 major epicardial coronary artery shown on coronary angiography
2.3. Current stable angina with both of the following:
2.3.1. Current and typical clinical history
2.3.2. A >50% stenosis in >=1 major epicardial coronary artery shown on coronary
angiography
3. Impaired glucose tolerance diagnosed on a single 75 g anhydrous glucose OGTT, defined as a 2-hour plasma glucose (2HPG) value >=7.8 but <=11.1 mmol/l and a fasting plasma glucose (FPG) <7.0 mmol/l
4. Optimised cardiovascular drug therapy
5. At least 80% adherent to single-blind placebo Study Medication during the run-in period
6. Provision of written informed consent
Exclusion criteria: Current information as of 02/03/10:
1. Previous history of diabetes, other than gestational diabetes.
2. MI, unstable angina, stroke or a transient ischaemic attack (TIA) within the previous three months.
3. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention.
4. New York Heart Association (NYHA) class III or IV heart failure.
5. Evidence of severe hepatic disease.
6. Evidence of severe renal impairment or an eGFR <30 ml/min/1.73m2 (derived using the MDRD Chinese equation)
7. Any other condition likely to reduce adherence to the protocol e.g. alcoholism, major active psychiatric disorder, cognitive impairment or a condition likely to markedly limit life expectancy e.g. malignancy.
8. Pregnancy (or planned pregnancy within the next five years).
9. Concurrent participation in any other clinical interventional trial.
10. Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems.
11. Thought by the investigator for any reason to be unsuitable for participation in this clinical study.

Initial information at time of registration:
1. Previous history of diabetes, other than gestational diabetes
2. MI, stroke or a transient ischaemic attack (TIA) within the previous three months
3. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention
4. New York Heart Association (NYHA) class III or IV heart failure
5. Evidence of severe hepatic disease
6. Evidence of severe renal impairment or an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m^2 (derived using the MDRD Chinese equation)
7. Any other condition likely to reduce adherence to the protocol e.g., alcoholism, major active psychiatric disorder, cognitive impairment or a condition likely to markedly limit life expectancy e.g., malignancy
8. Pregnancy (or planned pregnancy within the next five years)
9. Concurrent participation in any other clinical interventional trial
10. Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems
11. Thought by the investigator for any reason to be unsuitable for participation in this clinical study

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Coronary heart disease, acute coronary syndrome, impaired glucose tolerance, type 2 diabetes mellitus

Intervention(s)

Acarbose (oral) vs placebo.

The participants in the intervention group will be given one tablet (50 mg) of acarbose per day to be taken with a meal during the first week (7 days). During the second week, the dose is increased to two tablets/day (50 mg twice a day; 100 mg/day), and then three tablets/day (50 mg three times a day; 150 mg/day) thereafter. The maximum tolerated dose will be taken for the duration of the trial (maximum dose is 150 mg/day).

Total duration of interventions: Approximately four years

Primary Outcome(s)

Occurrence of any one of the following:
1. Cardiovascular death
2. Non-fatal MI
3. Non-fatal stroke

The primary and secondary outcomes will be monitored for a minimum of 4 years/participant. The outcomes will be assessed at 1, 2 and 4 months post-randomisation, and then every 4 months thereafter for the remainder of the trial.

Secondary Outcome(s)

Current information as of 02/03/10:
1. 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), with no intervening non-diagnostic values
2. All cause mortality
3. 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.
4. Proportion of patients with evidence of non-alcoholic fatty liver disease (NAFLD) as judged by changes in ALT levels
5. Proportion of patients with an impaired renal function as evidenced by:
A reduced eGFR (<30 ml/minute/ 1.73 m2) estimated using the Chinese MDRD formula, or a doubling of the baseline plasma creatinine level, or a halving of the baseline eGRF

The primary and secondary outcomes will be monitored for a minimum of 4 years/participant. The outcomes will be assessed at 1, 2 and 4 months post-randomisation, and then every 4 months thereafter for the remainder of the trial.

Initial information at time of registration:
1. 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), with no intervening non-diagnostic values
2. All cause mortality
3. 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.
4. Proportion of patients with evidence of non-alcoholic fatty liver disease (NAFLD) as judged by changes in alanine aminotransferase (ALT) levels
5. Proportion of patients with an impaired renal function as evidenced by a reduced eGFR (<60 ml/minute/1.73 m^2) estimated using the Chinese MDRD formula, or a doubling of the baseline plasma creatinine level

The primary and secondary outcomes will be monitored for a minimum of 4 years/participant. The outcomes will be assessed at 1, 2 and 4 months post-randomisation, and then every 4 months thereafter for the remainder of the trial.

Secondary ID(s)

11232

NCT00829660

Source(s) of Monetary Support

Bayer Schering Pharma (UK)

Secondary Sponsor(s)

N/A