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| [ ...Back to search results ] | [ Print-friendly version ] |
| Acarbose Cardiovascular Evaluation Trial |
| ISRCTN | ISRCTN91899513 |
| ClinicalTrials.gov identifier | NCT00829660 |
| Public title | Acarbose Cardiovascular Evaluation Trial |
| 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 |
| Acronym | ACE |
| Serial number at source | 11232 |
| Study hypothesis |
To determine whether acarbose therapy can reduce cardiovascular-related morbidity and mortality in patients with impaired glucose intolerance (IGT) who have established coronary heart disease (CHD) 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.
Please note that this trial is recruiting as of 20/04/2009. The first participant was enrolled on 17/02/2009 and randomised on 20/03/2009. Please note that as of 02/03/10 this trial has been updated. All updates can be found in the relavent field with the above update date. Changes to the protocol were approved by OXTREC. Please note that as of 21/09/2011 this trial record has again been updated. All updates can be found in the relavent field with the aforementioned date. Changes to the protocol were approved by OXTREC. |
| Lay summary | Not provided at time of registration |
| Ethics approval | Oxford Tropical Research Ethics Committee (OXTREC) on 28/10/2008 (ref: 51 08). Amendments to protocol were approved on the 17/02/2010. Further amendments to protocol approved on 18/08/2011. |
| Study design | Phase IV multi-centre double-blind randomised controlled clinical outcome trial |
| Countries of recruitment | China |
| Disease/condition/study domain | Coronary heart disease, acute coronary syndrome, impaired glucose tolerance, type 2 diabetes mellitus |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 15/12/2008 |
| Anticipated end date | 31/10/2014 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 7,500 |
| Interventions |
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 measure(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 measure(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. |
| Sources of funding | Bayer Schering Pharma (UK) |
| Trial website | http://www.dtu.ox.ac.uk/ace |
| Publications | |
| Contact name | Prof Rury Holman |
| Address |
Diabetes Trials Unit
Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) Churchill hospital Old Road Headington |
| City/town | Oxford |
| Zip/Postcode | OX3 7LJ |
| Country | United Kingdom |
| Tel | +44 (0)1865 857240 |
| Fax | +44 (0)1865 857241 |
| ace@dtu.ox.ac.uk | |
| Sponsor | University of Oxford (UK) |
| Address |
University Offices
Wellington Square |
| City/town | Oxford |
| Zip/Postcode | OX1 2JD |
| Country | United Kingdom |
| research.services@admin.ox.ac.uk | |
| Sponsor website: | http://www.ox.ac.uk |
| Date applied | 03/11/2008 |
| Last edited | 21/09/2011 |
| Date ISRCTN assigned | 12/11/2008 |
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| © 2012 ISRCTN unless otherwise stated. | |
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