Acarbose Cardiovascular Evaluation Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine whether acarbose therapy can reduce cardiovascular-related morbidity and mortality in patients with impaired glucose tolerance (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.

Detailed Description
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A long-term, 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.

Official Title
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A Long-term, 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

Conditions
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Coronary Heart Disease, Acute Coronary Syndrome, Impaired Glucose Tolerance, Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: Acarbose
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 50 years or more. Definite CHD, defined as a, b or c below: Previous myocardial infarction (MI) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following: Typical clinical presentation Confirmatory ECG changes Appropriate elevation of cardiac enzymes/biomarkers Previous unstable angina (UA) or Acute Coronary Syndrome (ACS), but not within the last 3 months, with any two of the following: Typical clinical presentation Confirmatory ECG changes 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. Current stable angina defined as: Typical clinical history with symptoms occurring within the last month, and 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. Impaired glucose tolerance diagnosed on a single standard oral glucose tolerance test (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. Optimised cardiovascular drug therapy. At least 80% adherent to single blind placebo Study Medication during the run-in period. Provision of written informed consent. Exclusion Criteria: Previous history of diabetes, other than gestational diabetes. MI, unstable angina, stroke or a transient ischaemic attack (TIA) within the previous three months. Planned or anticipated coronary, cerebrovascular or peripheral arterial revascularisation or other major surgical intervention, at the time of randomisation New York Heart Association (NYHA) class III or IV heart failure. Evidence of severe hepatic disease. Evidence of severe renal impairment or an eGFR <30 ml/min/1.73m2 (derived using the Modification of Diet in Renal Disease, MDRD, Chinese equation) 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. Pregnancy (or planned pregnancy within the next five years). Concurrent participation in any other clinical interventional trial. Note: Patients who were treated previously with an alphaglucosidase inhibitor must have at least a three-month washout period before being randomised into the ACE trial. Known intolerance to alpha glucosidase inhibitors or gastrointestinal problems. Thought by the investigator for any reason to be unsuitable for participation in this clinical study.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acarbose<br>The participants were given one tablet (50mg) of acarbose per day, taken with a meal during their first week (7 days). During the second week, the dose was increased to two tablets/day (50mg twice a day i.e. 100mg/day) and then three tablets/day (50mg three times a day i.e. 150mg/day) thereafter. The maximum tolerated dose is being taken for the duration of the trial (maximum dose is 150mg/day). | Drug: Acarbose<br>* The participants were given one tablet (50mg) of acarbose per day, taken with a meal during their first week (7 days). During the second week, the dose was increased to two tablets/day (50mg twice a day i.e. 100mg/day) and then three tablets/day (50mg three times a day i.e. 150mg/day) thereafter. The maximum tolerated dose is being taken for the duration of the trial (maximum dose is 150mg/day).<br>* Other names: Glucobay;|
| Placebo Comparator: Matching Placebo<br>The participants were given one tablet of matching placebo per day, taken with a meal during their first week (7 days). During the second week, the dose was increased to two tablets/day and then three tablets/day thereafter. The maximum tolerated dose is being taken for the duration of the trial (maximum dose is 3 tablets/day). | Drug: Matching Placebo<br>* The participants were given one tablet of matching placebo per day, taken with a meal during their first week (7 days). During the second week, the dose was increased to two tablets/day and then three tablets/day thereafter. The maximum tolerated dose is being taken for the duration of the trial (maximum dose is 3 tablets/day).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite cardiovascular outcome defined as the time after randomisation to the first occurrence of any one of the following: -Cardiovascular death -Non-fatal MI -Non-fatal stroke -Hospitalisation for Unstable Angina -Hospitalisation for Heart Failure |  | Follow-up until 728 adjudicated Primary Outcome Measures have been recorded | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |  | 
| All cause mortality |  |  | 
| Each of the components of the primary composite cardiovascular outcome will also be analysed individually, both as first and as total events. |  |  | 
| Major Cardiovascular Event (MACE) composite cardiovascular outcome, defined as the time after randomisation to the first occurrence of any one of the following: - Cardiovascular death - Non-fatal MI - Non-fatal stroke |  |  | 
| Impaired renal function as evidenced by: A reduced estimate of glomerular filtration rate( eGFR <30 ml/minute/ 1.73 m2) estimated using the Chinese MDRD formula, a doubling of the baseline plasma creatinine level, a halving of the baseline eGFR |  |  | 
| Resource use, costs and cost effectiveness |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acarbose