Overview

This trial is active, not recruiting.

Conditions coronary heart disease, acute coronary syndrome, impaired glucose tolerance, type 2 diabetes mellitus (t2dm)
Treatments acarbose, matching placebo
Phase phase 4
Sponsor University of Oxford
Collaborator Bayer
Start date February 2009
End date July 2017
Trial size 6526 participants
Trial identifier NCT00829660, 11232, ISRCTN91899513

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Active Comparator)
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).
acarbose Glucobay
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).
(Placebo Comparator)
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).
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).

Primary Outcomes

Measure
A composite cardiovascular outcome defined as the time to first occurrence of any one of the following:; - Cardiovascular death - Non-fatal MI - Non-fatal stroke - Hospitalisation for Unstable Angina - Hospitalisation for Heart Failure
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded

Secondary Outcomes

Measure
Transition to type 2 diabetes
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.
All cause mortality
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.
Major Cardiovascular Event (MACE) composite cardiovascular outcome, defined as the time to first occurrence of any one of the following: - Cardiovascular death - Non-fatal MI - Non-fatal stroke
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.
Evidence of NAFLD
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.
Impaired renal function
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.
Resource use, costs and cost effectiveness
time frame: Follow-up until 904 adjudicated Primary Outcome Measures have been recorded.

Eligibility Criteria

Male or female participants at least 50 years old.

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 (Note: Patients with stents are eligible): - 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 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. - 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. - 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 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. - 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.

Additional Information

Official title 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
Principal investigator Professor Rury R Holman, FRCP FMedSci
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by University of Oxford.