Acarbose Cardiovascular Evaluation Trial

Acute Coronary Syndrome Clinical Trial

— ACE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00829660
• Other study ID #: 11232
• Secondary ID: ISRCTN91899513
• Status: Completed
• Phase: Phase 4
• First received: January 26, 2009
• Last updated: July 21, 2017
• Start date: February 17, 2009
• Est. completion date: April 18, 2017

Study information

• Verified date: July 2017
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6526
• Est. completion date: April 18, 2017
• Est. primary completion date: April 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Heart Diseases
• Impaired Glucose Tolerance
• Myocardial Ischemia
• Syndrome
• Type 2 Diabetes Mellitus (T2DM)

Intervention

Drug:
• 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).
• 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).

Locations

Country	Name	City	State
China	The Central Hospital of Anshan	Anshan	Liaoning
China	Baotou Central Hospital	Baotou	Inner Mongolia
China	The First Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Aerospace 731 Hospital	Beijing	Beijing
China	Aerospace Central Hospital	Beijing	Beijing
China	Affiliated to The Capital University of Medical Sciences Beijing Friendship Hospital	Beijing	Beijing
China	Anzhen Hospital of The Capital University of Medical Sciences 2nd.	Beijing	Beijing
China	Beijing Anzhen Hospital of The Capital University of Medical Sciences	Beijing	Beijing
China	Beijing Chuiyangliu Hospital	Beijing	Beijing
China	Beijing Healthy Palace Hospital	Beijing	Beijing
China	Beijing Ji Shui Tan Hospital	Beijing	Beijing
China	Beijing Pinggu Hospital	Beijing	Beijing
China	Beijing Shijingshan Hospital	Beijing	Beijing
China	Beijing Shijitan Hospital	Beijing	Beijing
China	Beijing Yanhua Hospital	Beijing	Beijing
China	China Meitan General Hospital	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Fu Xing Hospital	Beijing	Beijing
China	General Hospital of Second Artillery PLA	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	PLA General Hospital	Beijing	Beijing
China	Wangjing Hospital of CACMS	Beijing	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	China-Japan Union Hospital of Jilin University	Changchun	Jilin
China	The Second Hospital of Jilin University	Changchun	Jilin
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	The Fourth Hospital of Changsha	Changsha	Hunan
China	The Third Hospital of Changsha	Changsha	Hunan
China	Xiangya Hospital Central-South University	Changsha	Hunan
China	Chengdu First People's Hospital	Chengdu	Sichuan
China	Chengdu Second People's Hospital	Chengdu	Sichuan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	The West China Hospital	Chengdu	Sichuan
China	Chifeng Municipal Hospital	Chifeng	Inner Mongolia
China	Chongqing Medical University Second Afflicated Hospital	Chongqing	Chongqing
China	Chongqing Third People's Hospital	Chongqing	Chongqing
China	Chongqing Zhongshan Hospital	Chongqing	Chongqing
China	Da Ping Hospital	Chongqing	Chongqing
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Second People's Hospital of Chongqing	Chongqing	Chongqing
China	Da Qing Oilfield General Hospital	Da Qing	Heilongjiang
China	Affiliated Zhongshan Hospital of Dalian University	Dalian	Liaoning
China	Dalian Central Hospital	Dalian	Liaoning
China	The First Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	The People's Hospital of Fujian Province	Fuzhou	Fujian
China	Union Hospital Affiliated to Fujian Medical University	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Guangzhou Medical College	Guangzhou	Guangdong
China	Wu Jing Zhong Dui Hospital of Guangdong Province	Guangzhou	Guangdong
China	The Affiliated Hospital of Guiyang Medical College	Guiyang	Guizhou
China	Sir Run Run Shaw Hospital Affiliated With School of Medicine, Zhe Jiang University	Hangzhou	Zhejiang
China	Zhe Jiang Hospital	Hangzhou	Zhejiang
China	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Inner Mongolia Hospital	Hohhot	Inner Mongolia
China	The Central Hospital of Jinan	Jinan	Shandong
China	The First People's Hospital of Jinan	Jinan	Shandong
China	The General Hospital of Jinan Military Region	Jinan	Shandong
China	Jiujiang University Hospital	Jiujiang	Jiangxi
China	The First Affiliated Hospital of Kunming Medical College	Kunming	Yunnan
China	The First People's Hospital of Yunnan Province	Kunming	Yunnan
China	The Second Affiliated Hospital of Kunming Medical College	Kunming	Yunnan
China	Linyi People's Hospital	Linyi	Shandong
China	Liuzhou People's Hospital	Liuzhou	Guangxi
China	Liuzhou Worker's Hospital	Liuzhou	Guangxi
China	Luo Yang Central Hospital, Affiliated to Zhengzhou University	Luoyang	Henan
China	The First Affiliated Hospital of Henan Science & Technology University	Luoyang	Henan
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	81st Hospital of Chinese PLA	NanJing	Jiangsu
China	BENQ Hospital	Nanjing	Jiangsu
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Jiangsu Province Official Hospital	NanJing	Jiangsu
China	Jiangsu Provincial Hospital of TCM	NanJing	Jiangsu
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Nanjing Jiangning Hospital	Nanjing	Jiangsu
China	Nanjing Zhongda Hospital	Nanjing	Jiangsu
China	303 Hospital of People's Liberation Army	Nanning	Guangxi
China	Minzu Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Hospital Affiliated of Medical School, Qingdao University	Qingdao	Shandong
China	The Qingdao Municiple Hospital	Qingdao	Shandong
China	Changhai Hospital	Shanghai	Shanghai
China	Number 411 Hospital of PLA	Shanghai	Shanghai
China	Putuo District Center Hospital	Shanghai	Shanghai
China	Renji Hospital Affilicated to Jiaotong University School of Medicine	Shanghai	Shanghai
China	Ruijin Hospital Affiliated to the Shanghai Jiaotong University Medical School	Shanghai	Shanghai
China	Shanghai Central Hospital of Xuhui District	Shanghai	Shanghai
China	Shanghai Central Hospital of Yangpu District	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shanghai Huadong Hospital	Shanghai	Shanghai
China	Shanghai Jinshan Hospital	Shanghai	Shanghai
China	Shanghai Ninth People's Hospital	Shanghai	Shanghai
China	Shanghai Pudong New Area Gongli Hospital	Shanghai	Shanghai
China	Shanghai Pudong New District People's Hospital	Shanghai	Shanghai
China	Shanghai Putuo District People's Hospital	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Shanghai Zhabei District Shibei Hospital	Shanghai	Shanghai
China	Shanghai Zhongshan Hospital	Shanghai	Shanghai
China	Tongji Hospital of Tongji University	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Xianyang Central Hospital	Shengyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	The Fourth Hospital of China Medical University	Shenyang	Liaoning
China	The People's Hospital of Liaoning Province	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Qingdao Fuwai Hospital	Shibei	Shandong
China	First Affiliated Hospital of the Medical College	Shihezi	Xinjiang
China	Bethune International Peace Hospital	Shijiazhuang	Hebei
China	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Sichuan Mianyang 404 Hospital	Sichuan	Sichuan
China	Suzhou Municipal Hospital	Suzhou	Jiangsu
China	Taian City Central Hospital	Taian	Shandong
China	General Hospital of Tisco	Taiyuan	Shanxi
China	Shanxi Cardiovascular Hospital	Taiyuan	Shanxi
China	Taiyuan City Central Hospital	Taiyuan	Shanxi
China	The Third Engineering Bureau Hospital of Ministry of Railway	Taiyuan	Shanxi
China	Tangshan Workers Hospital	Tangshan	Hebei
China	The Affiliated Hospital of North China Coal Medical University	Tangshan	Hebei
China	Yu Tian County Hospital	Tangshan	Hebei
China	Army Police's Medical College Affiliated Hospital	Tianjin	Tianjin
China	Dagang Oil-Field General Hospital	Tianjin	Tianjin
China	The Fifth Central Hospital of Tianjin	Tianjin	Tianjin
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Chest Hospital	Tianjin	Tianjin
China	Tianjin First Center Hospital	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	Tianjin Union Hospital	Tianjin	Tianjin
China	Tianjin Union Medicine Centre	Tianjin	Tianjin
China	General Hospital of Xinjiang Production and Construction Corps	Urumqi	Xinjiang
China	The 474th Hospital of PLA	Urumqi	Xinjiang
China	The First Teaching Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Xin Jiang Traditional Chinese Medicine Hospital	Urumqi	Xinjiang
China	Pu'ai Hospital of Wuhan City	Wuhan	Hubei
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Tongji Hospital of Tongji Medical College of Huazhong	Wuhan	Hubei
China	Union Hospital of Tongji Medical College of Huazhong	Wuhan	Hubei
China	Wuhan Asia Heart Hospital	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Wuxi No.2 People's Hospital	Wuxi	Jiangsu
China	Wuxi No.3 People's Hospital	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	Affiliated Hospital of Xi'an Medical college	Xi'an	Shaanxi
China	PLA No.323 Hospital	Xi'an	Shanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Xi'an Central Hospital	Xi'an	Shaanxi
China	The First Hospital of Xiamen	Xiamen	Fujian
China	Zhongshan Hospital Xiamen University	Xiamen	Fujian
China	Hospital Affiliated Xuzhou Medical University	Xuzhou	Jiangsu
China	The Second Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Affiliated Hospital of Yan'an University	Yan'an	Shaanxi
China	Yan'an People's Hospital	Yanan	Shaanxi
China	Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The First Hospital of Yinchuan	Yinchuan	Ningxia
China	The People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia
China	The First Hospital of Yulin	Yulin	Shaanxi
China	People's Hospital of Yuxi City	Yuxi	Yunnan
China	The Third Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei
China	The First Affiliated Hospital of Henan College of TCM	Zhengzhou	Henan
China	The People's Hospital of Zhengzhou	Zhengzhou	Henan
China	The Second Affiliated Hospital of Zhengzhou University	ZhengZhou	Henan
China	Zhenjiang First People's Hospital	Zhenjiang	Jiangsu
China	Zhong Shan City People's Hospital	Zhongshan	Guangdong
China	The Fifth Affiliated Hospital of Sun Yat-Sen University	Zhuhai	Guangdong
Hong Kong	Prince of Wales Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Bayer

Countries where clinical trial is conducted

China,  Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	All cause mortality
Secondary	Each of the components of the primary composite cardiovascular outcome will also be analysed individually, both as first and as total events.
Secondary	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
Secondary	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
Secondary	Resource use, costs and cost effectiveness

External Links

•   Diabetes Trials Unit, International Co-ordinating Centre for the ACE Trial