Clinical trial NCT00829660: Acarbose Cardiovascular Evaluation Trial
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Heart Disease
Acute Coronary Syndrome
Impaired Glucose Tolerance
Type 2 Diabetes Mellitus (T2DM)
Keywords: Acarbose
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2009-01-27
Enrollment: 6526
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Follow-up until 728 adjudicated Primary Outcome Measures have been recorded
Secondary outcomes:
measure: 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.
measure: All cause mortality
measure: Each of the components of the primary composite cardiovascular outcome will also be analysed individually, both as first and as total events.
measure: 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
measure: 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
measure: Resource use, costs and cost effectiveness
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Chuiyangliu Hospital
state: Beijing
city: Beijing
country: China
facility: China Meitan General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Anzhen Hospital of The Capital University of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Ji Shui Tan Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan Hospital
state: Beijing
city: Beijing
country: China
facility: Fu Xing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijingshan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Aerospace Central Hospital
state: Beijing
city: Beijing
country: China
facility: Affiliated to The Capital University of Medical Sciences Beijing Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Wangjing Hospital of CACMS
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Healthy Palace Hospital
state: Beijing
city: Beijing
country: China
facility: Aerospace 731 Hospital
state: Beijing
city: Beijing
country: China
facility: General Hospital of Second Artillery PLA
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Anzhen Hospital of The Capital University of Medical Sciences 2nd.
state: Beijing
city: Beijing
country: China
facility: Beijing Pinggu Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Yanhua Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Medical University Second Afflicated Hospital
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Zhongshan Hospital
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Third People's Hospital
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Da Ping Hospital
state: Chongqing
city: Chongqing
country: China
facility: The Second People's Hospital of Chongqing
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
state: Fujian
city: Fuzhou
country: China
facility: Union Hospital Affiliated to Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: The People's Hospital of Fujian Province
state: Fujian
city: Xiamen
country: China
facility: The First Hospital of Xiamen
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical College
state: Guangdong
city: Guangzhou
country: China
facility: Wu Jing Zhong Dui Hospital of Guangdong Province
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Zhong Shan City People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou Worker's Hospital
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Nanning
country: China
facility: Minzu Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Nanning
country: China
facility: 303 Hospital of People's Liberation Army
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guiyang Medical College
state: Guizhou
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Bethune International Peace Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers Hospital
state: Hebei
city: Tangshan
country: China
facility: The Affiliated Hospital of North China Coal Medical University
state: Hebei
city: Tangshan
country: China
facility: Yu Tian County Hospital
state: Hebei
city: Zhangjiakou
country: China
facility: The Third Affiliated Hospital of Hebei North University
state: Hebei
city: Da Qing
country: China
facility: Da Qing Oilfield General Hospital
state: Heilongjiang
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan Science & Technology University
state: Henan
city: Luoyang
country: China
facility: Luo Yang Central Hospital, Affiliated to Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan College of TCM
state: Henan
city: Zhengzhou
country: China
facility: The People's Hospital of Zhengzhou
state: Henan
city: ZhengZhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College of Huazhong
state: Hubei
city: Wuhan
country: China
facility: Wuhan Asia Heart Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of Huazhong
state: Hubei
city: Wuhan
country: China
facility: Pu'ai Hospital of Wuhan City
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: The Fourth Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central-South University
state: Hunan
city: Changsha
country: China
facility: The Third Hospital of Changsha
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
state: Inner Mongolia
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
state: Inner Mongolia
city: Hohhot
country: China
facility: Inner Mongolia Hospital
state: Inner Mongolia
city: NanJing
country: China
facility: 81st Hospital of Chinese PLA
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Zhongda Hospital
state: Jiangsu
city: Nanjing
country: China
facility: BENQ Hospital
state: Jiangsu
city: NanJing
country: China
facility: Jiangsu Province Official Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: NanJing
country: China
facility: Jiangsu Provincial Hospital of TCM
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi No.2 People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi No.3 People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Hospital Affiliated Xuzhou Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: The Second Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Zhenjiang
country: China
facility: Zhenjiang First People's Hospital
state: Jiangsu
city: Jiujiang
country: China
facility: Jiujiang University Hospital
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Third Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Anshan
country: China
facility: The Central Hospital of Anshan
state: Liaoning
city: Dalian
country: China
facility: Affiliated Zhongshan Hospital of Dalian University
state: Liaoning
city: Dalian
country: China
facility: The First Hospital of Dalian Medical University
state: Liaoning
city: Dalian
country: China
facility: Dalian Central Hospital
state: Liaoning
city: Shengyang
country: China
facility: Xianyang Central Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The People's Hospital of Liaoning Province
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The Fourth Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: The First Hospital of Yinchuan
state: Ningxia
city: Yinchuan
country: China
facility: Affiliated Hospital of Ningxia Medical University
state: Ningxia
city: Yinchuan
country: China
facility: The People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia
city: Xi'an
country: China
facility: Xi'an Central Hospital
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Affiliated Hospital of Xi'an Medical college
state: Shaanxi
city: Yan'an
country: China
facility: Affiliated Hospital of Yan'an University
state: Shaanxi
city: Yanan
country: China
facility: Yan'an People's Hospital
state: Shaanxi
city: Yulin
country: China
facility: The First Hospital of Yulin
state: Shaanxi
city: Jinan
country: China
facility: The Central Hospital of Jinan
state: Shandong
city: Jinan
country: China
facility: The First People's Hospital of Jinan
state: Shandong
city: Jinan
country: China
facility: The General Hospital of Jinan Military Region
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Hospital Affiliated of Medical School, Qingdao University
state: Shandong
city: Qingdao
country: China
facility: The Qingdao Municiple Hospital
state: Shandong
city: Shibei
country: China
facility: Qingdao Fuwai Hospital
state: Shandong
city: Taian
country: China
facility: Taian City Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to the Shanghai Jiaotong University Medical School
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Central Hospital of Xuhui District
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Huadong Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Putuo District People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Putuo District Center Hospital
state: Shanghai
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Number 411 Hospital of PLA
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Central Hospital of Yangpu District
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital Affilicated to Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong New Area Gongli Hospital
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhabei District Shibei Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jinshan Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pudong New District People's Hospital
state: Shanghai
city: Taiyuan
country: China
facility: General Hospital of Tisco
state: Shanxi
city: Taiyuan
country: China
facility: The Third Engineering Bureau Hospital of Ministry of Railway
state: Shanxi
city: Taiyuan
country: China
facility: Taiyuan City Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
state: Shanxi
city: Xi'an
country: China
facility: PLA No.323 Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu First People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: Chengdu Second People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: The West China Hospital
state: Sichuan
city: Sichuan
country: China
facility: Sichuan Mianyang 404 Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Union Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Chest Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Union Medicine Centre
state: Tianjin
city: Tianjin
country: China
facility: Army Police's Medical College Affiliated Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin First Center Hospital
state: Tianjin
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjin
city: Tianjin
country: China
facility: Dagang Oil-Field General Hospital
state: Tianjin
city: Tianjin
country: China
facility: The Fifth Central Hospital of Tianjin
state: Tianjin
city: Shihezi
country: China
facility: First Affiliated Hospital of the Medical College
state: Xinjiang
city: Urumqi
country: China
facility: Xin Jiang Traditional Chinese Medicine Hospital
state: Xinjiang
city: Urumqi
country: China
facility: General Hospital of Xinjiang Production and Construction Corps
state: Xinjiang
city: Urumqi
country: China
facility: The 474th Hospital of PLA
state: Xinjiang
city: Urumqi
country: China
facility: The First Teaching Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical College
state: Yunnan
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical College
state: Yunnan
city: Yuxi
country: China
facility: People's Hospital of Yuxi City
state: Yunnan
city: Hangzhou
country: China
facility: Zhe Jiang Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Affiliated With School of Medicine, Zhe Jiang University
state: Zhejiang
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Diabetes Trials Unit, University of Oxford
name: Professor Rury R Holman, FRCP FMedSci
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wamil M, McMurray JJV, Scott CAB, Coleman RL, Sun Y, Standl E, Ryden L, Holman RR. Predicting heart failure events in patients with coronary heart disease and impaired glucose tolerance: Insights from the Acarbose Cardiovascular Evaluation (ACE) trial. Diabetes Res Clin Pract. 2020 Dec;170:108488. doi: 10.1016/j.diabres.2020.108488. Epub 2020 Oct 6.
citation: Gerstein HC, Coleman RL, Scott CAB, Xu S, Tuomilehto J, Ryden L, Holman RR; ACE Study Group. Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People With Coronary Heart Disease and Impaired Glucose Tolerance: Insights From the ACE Trial. Diabetes Care. 2020 Sep;43(9):2242-2247. doi: 10.2337/dc19-2046. Epub 2020 Jul 8.
citation: Holman RR, Coleman RL, Chan JCN, Chiasson JL, Feng H, Ge J, Gerstein HC, Gray R, Huo Y, Lang Z, McMurray JJ, Ryden L, Schroder S, Sun Y, Theodorakis MJ, Tendera M, Tucker L, Tuomilehto J, Wei Y, Yang W, Wang D, Hu D, Pan C; ACE Study Group. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):877-886. doi: 10.1016/S2213-8587(17)30309-1. Epub 2017 Sep 13.