Acarbose Cardiovascular Evaluation Trial

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus (T2DM); Coronary Heart Disease; Acute Coronary Syndrome; Impaired Glucose Tolerance
• Interventions: Drug: Matching Placebo; Drug: Acarbose

• Registration Number: NCT00829660
• Lead Sponsor: University of Oxford

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-01-26
• Study First Submitted QC: 2009-01-26
• Study First Posted: 2009-01-27
• Study Start: 2009-02-17
• Primary Completion: 2017-04-11
• Study Completion: 2017-04-18
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-21
• Last Update Posted: 2017-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6526

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching Placebo	Matching Placebo	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).
Acarbose	Acarbose	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).

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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
All cause mortality

Trial Locations

Locations (176)

The First Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Beijing Chuiyangliu Hospital; 🇨🇳 Beijing, Beijing, China

China Meitan General Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Anzhen Hospital of The Capital University of Medical Sciences; 🇨🇳 Beijing, Beijing, China

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Ji Shui Tan Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Shijitan Hospital; 🇨🇳 Beijing, Beijing, China

Fu Xing Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Shijingshan Hospital; 🇨🇳 Beijing, Beijing, China

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