Acarbose Cardiovascular Evaluation Trial (ACE)

University of Oxford

Status and phase: Completed; Phase 4

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

Treatments: Drug: Matching Placebo; Drug: Acarbose

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00829660

ISRCTN91899513

11232

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 6,526 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female, aged 50 years or more.

• Definite CHD, defined as a, b or c below:

  1. 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

  2. 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.

  3. 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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6,526 participants in 2 patient groups, including a placebo group

Acarbose

Active Comparator group

Description:

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).

Treatment:

Drug: Acarbose

Matching Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Matching Placebo