ACE: Acarbose Cardiovascular Evaluation Trial

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT00829660

Collaborator

Bayer (Industry)

6,526

Enrollment

177

Locations

Arms

Actual Duration (Months)

36.9

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Heart Disease Acute Coronary Syndrome Impaired Glucose Tolerance Type 2 Diabetes Mellitus (T2DM)	Drug: Acarbose Drug: Matching Placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

6526 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Feb 17, 2009

Actual Primary Completion Date :

Apr 11, 2017

Actual Study Completion Date :

Apr 18, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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).	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). Other Names: Glucobay
Placebo Comparator: 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).	Drug: 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).

Arm

Intervention/Treatment

Active Comparator: 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).

Drug: Acarbose

Other Names:

Glucobay

Placebo Comparator: 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).

Drug: Matching Placebo

Outcome Measures

Primary Outcome Measures

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

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. []
All cause mortality []
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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, aged 50 years or more.
Definite CHD, defined as a, b or c below:

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

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China	230032
2	Beijing Chuiyangliu Hospital	Beijing	Beijing	China	100022
3	China Meitan General Hospital	Beijing	Beijing	China	100028
4	Beijing Anzhen Hospital of The Capital University of Medical Sciences	Beijing	Beijing	China	100029
5	China-Japan Friendship Hospital	Beijing	Beijing	China	100029
6	Peking University First Hospital	Beijing	Beijing	China	100034
7	Beijing Ji Shui Tan Hospital	Beijing	Beijing	China	100035
8	Beijing Shijitan Hospital	Beijing	Beijing	China	100038
9	Fu Xing Hospital	Beijing	Beijing	China	100038
10	Beijing Shijingshan Hospital	Beijing	Beijing	China	100043
11	Peking University People's Hospital	Beijing	Beijing	China	100044
12	Aerospace Central Hospital	Beijing	Beijing	China	100049
13	Affiliated to The Capital University of Medical Sciences Beijing Friendship Hospital	Beijing	Beijing	China	100050
14	Wangjing Hospital of CACMS	Beijing	Beijing	China	100053
15	Xuanwu Hospital Capital Medical University	Beijing	Beijing	China	100053
16	Beijing Healthy Palace Hospital	Beijing	Beijing	China	100054
17	Aerospace 731 Hospital	Beijing	Beijing	China	100074
18	General Hospital of Second Artillery PLA	Beijing	Beijing	China	100088
19	Peking Union Medical College Hospital	Beijing	Beijing	China	100730
20	PLA General Hospital	Beijing	Beijing	China	100853
21	Anzhen Hospital of The Capital University of Medical Sciences 2nd.	Beijing	Beijing	China	101200
22	Beijing Pinggu Hospital	Beijing	Beijing	China	101200
23	Beijing Yanhua Hospital	Beijing	Beijing	China	102500
24	Chongqing Medical University Second Afflicated Hospital	Chongqing	Chongqing	China	400010
25	Chongqing Zhongshan Hospital	Chongqing	Chongqing	China	400013
26	Chongqing Third People's Hospital	Chongqing	Chongqing	China	400014
27	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400016
28	Da Ping Hospital	Chongqing	Chongqing	China	400042
29	The Second People's Hospital of Chongqing	Chongqing	Chongqing	China	402160
30	Fujian Provincial Hospital	Fuzhou	Fujian	China	350001
31	Union Hospital Affiliated to Fujian Medical University	Fuzhou	Fujian	China	350001
32	The People's Hospital of Fujian Province	Fuzhou	Fujian	China	350004
33	The First Hospital of Xiamen	Xiamen	Fujian	China	361003
34	Zhongshan Hospital Xiamen University	Xiamen	Fujian	China	361004
35	Guangdong General Hospital	Guangzhou	Guangdong	China	510080
36	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong	China	510080
37	The First Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510080
38	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510120
39	The Third Affiliated Hospital of Guangzhou Medical College	Guangzhou	Guangdong	China	510150
40	Wu Jing Zhong Dui Hospital of Guangdong Province	Guangzhou	Guangdong	China	510507
41	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong	China	510630
42	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China	518036
43	Zhong Shan City People's Hospital	Zhongshan	Guangdong	China	528403
44	The Fifth Affiliated Hospital of Sun Yat-Sen University	Zhuhai	Guangdong	China	519000
45	Liuzhou Worker's Hospital	Liuzhou	Guangxi	China	545005
46	Liuzhou People's Hospital	Liuzhou	Guangxi	China	545006
47	Minzu Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi	China	530001
48	303 Hospital of People's Liberation Army	Nanning	Guangxi	China	530021
49	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi	China	530021
50	The Affiliated Hospital of Guiyang Medical College	Guiyang	Guizhou	China	550004
51	Cangzhou Central Hospital	Cangzhou	Hebei	China	062650
52	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050000
53	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050031
54	Bethune International Peace Hospital	Shijiazhuang	Hebei	China	050082
55	Tangshan Workers Hospital	Tangshan	Hebei	China	063000
56	The Affiliated Hospital of North China Coal Medical University	Tangshan	Hebei	China	063000
57	Yu Tian County Hospital	Tangshan	Hebei	China	064100
58	The Third Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei	China	075000
59	Da Qing Oilfield General Hospital	Da Qing	Heilongjiang	China	163001
60	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang	China	150001
61	The First Affiliated Hospital of Henan Science & Technology University	Luoyang	Henan	China	471003
62	Luo Yang Central Hospital, Affiliated to Zhengzhou University	Luoyang	Henan	China	471009
63	The First Affiliated Hospital of Henan College of TCM	Zhengzhou	Henan	China	450000
64	The People's Hospital of Zhengzhou	Zhengzhou	Henan	China	450003
65	The Second Affiliated Hospital of Zhengzhou University	ZhengZhou	Henan	China	450014
66	Union Hospital of Tongji Medical College of Huazhong	Wuhan	Hubei	China	430022
67	Wuhan Asia Heart Hospital	Wuhan	Hubei	China	430022
68	Tongji Hospital of Tongji Medical College of Huazhong	Wuhan	Hubei	China	430030
69	Pu'ai Hospital of Wuhan City	Wuhan	Hubei	China	430033
70	Renmin Hospital of Wuhan University	Wuhan	Hubei	China	430060
71	Zhongnan Hospital of Wuhan University	Wuhan	Hubei	China	430071
72	Hunan Provincial People's Hospital	Changsha	Hunan	China	410005
73	The Fourth Hospital of Changsha	Changsha	Hunan	China	410006
74	Xiangya Hospital Central-South University	Changsha	Hunan	China	410008
75	The Third Hospital of Changsha	Changsha	Hunan	China	410015
76	The First Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia	China	014010
77	Baotou Central Hospital	Baotou	Inner Mongolia	China	014040
78	Chifeng Municipal Hospital	Chifeng	Inner Mongolia	China	024000
79	Inner Mongolia Hospital	Hohhot	Inner Mongolia	China	010017
80	81st Hospital of Chinese PLA	NanJing	Jiangsu	China	210002
81	Nanjing First Hospital	Nanjing	Jiangsu	China	210006
82	Nanjing Drum Tower Hospital	Nanjing	Jiangsu	China	210008
83	Nanjing Zhongda Hospital	Nanjing	Jiangsu	China	210009
84	BENQ Hospital	Nanjing	Jiangsu	China	210017
85	Jiangsu Province Official Hospital	NanJing	Jiangsu	China	210024
86	Jiangsu Province Hospital	Nanjing	Jiangsu	China	210029
87	Jiangsu Provincial Hospital of TCM	NanJing	Jiangsu	China	210029
88	Nanjing Jiangning Hospital	Nanjing	Jiangsu	China	211100
89	Suzhou Municipal Hospital	Suzhou	Jiangsu	China	215000
90	Wuxi No.2 People's Hospital	Wuxi	Jiangsu	China	214002
91	Wuxi People's Hospital	Wuxi	Jiangsu	China	214023
92	Wuxi No.3 People's Hospital	Wuxi	Jiangsu	China	214041
93	Hospital Affiliated Xuzhou Medical University	Xuzhou	Jiangsu	China	221000
94	The Second Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu	China	221006
95	Zhenjiang First People's Hospital	Zhenjiang	Jiangsu	China	212002
96	Jiujiang University Hospital	Jiujiang	Jiangxi	China	332000
97	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi	China	330006
98	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
99	The Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330008
100	China-Japan Union Hospital of Jilin University	Changchun	Jilin	China	130033
101	The Second Hospital of Jilin University	Changchun	Jilin	China	130041
102	The Central Hospital of Anshan	Anshan	Liaoning	China	114001
103	Affiliated Zhongshan Hospital of Dalian University	Dalian	Liaoning	China	116001
104	The First Hospital of Dalian Medical University	Dalian	Liaoning	China	116011
105	Dalian Central Hospital	Dalian	Liaoning	China	116033
106	Xianyang Central Hospital	Shengyang	Liaoning	China	712000
107	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110004
108	The People's Hospital of Liaoning Province	Shenyang	Liaoning	China	110016
109	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110021
110	The Fourth Hospital of China Medical University	Shenyang	Liaoning	China	110032
111	The First Hospital of Yinchuan	Yinchuan	Ningxia	China	750001
112	Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750004
113	The People's Hospital of Ningxia Hui Autonomous Region	Yinchuan	Ningxia	China	750021
114	Xi'an Central Hospital	Xi'an	Shaanxi	China	710003
115	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710061
116	Affiliated Hospital of Xi'an Medical college	Xi'an	Shaanxi	China	710077
117	Affiliated Hospital of Yan'an University	Yan'an	Shaanxi	China	716000
118	Yan'an People's Hospital	Yanan	Shaanxi	China	716000
119	The First Hospital of Yulin	Yulin	Shaanxi	China	719000
120	The Central Hospital of Jinan	Jinan	Shandong	China	250013
121	The First People's Hospital of Jinan	Jinan	Shandong	China	250013
122	The General Hospital of Jinan Military Region	Jinan	Shandong	China	250031
123	Linyi People's Hospital	Linyi	Shandong	China	276003
124	Hospital Affiliated of Medical School, Qingdao University	Qingdao	Shandong	China	266003
125	The Qingdao Municiple Hospital	Qingdao	Shandong	China	266011
126	Qingdao Fuwai Hospital	Shibei	Shandong	China	266034
127	Taian City Central Hospital	Taian	Shandong	China	271000
128	Shanghai Ninth People's Hospital	Shanghai	Shanghai	China	200011
129	Ruijin Hospital Affiliated to the Shanghai Jiaotong University Medical School	Shanghai	Shanghai	China	200025
130	Shanghai Central Hospital of Xuhui District	Shanghai	Shanghai	China	200031
131	Shanghai Zhongshan Hospital	Shanghai	Shanghai	China	200032
132	Shanghai Huadong Hospital	Shanghai	Shanghai	China	200040
133	Shanghai Putuo District People's Hospital	Shanghai	Shanghai	China	200060
134	Putuo District Center Hospital	Shanghai	Shanghai	China	200062
135	Tongji Hospital of Tongji University	Shanghai	Shanghai	China	200065
136	Shanghai Tenth People's Hospital	Shanghai	Shanghai	China	200072
137	Number 411 Hospital of PLA	Shanghai	Shanghai	China	200081
138	Shanghai Central Hospital of Yangpu District	Shanghai	Shanghai	China	200090
139	Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200092
140	Shanghai East Hospital	Shanghai	Shanghai	China	200120
141	Renji Hospital Affilicated to Jiaotong University School of Medicine	Shanghai	Shanghai	China	200127
142	Shanghai Pudong New Area Gongli Hospital	Shanghai	Shanghai	China	200135
143	Changhai Hospital	Shanghai	Shanghai	China	200433
144	Shanghai Zhabei District Shibei Hospital	Shanghai	Shanghai	China	200435
145	Shanghai Jinshan Hospital	Shanghai	Shanghai	China	200540
146	Shanghai Pudong New District People's Hospital	Shanghai	Shanghai	China	201200
147	General Hospital of Tisco	Taiyuan	Shanxi	China	030003
148	The Third Engineering Bureau Hospital of Ministry of Railway	Taiyuan	Shanxi	China	030006
149	Taiyuan City Central Hospital	Taiyuan	Shanxi	China	030009
150	Shanxi Cardiovascular Hospital	Taiyuan	Shanxi	China	030024
151	PLA No.323 Hospital	Xi'an	Shanxi	China	710054
152	Chengdu First People's Hospital	Chengdu	Sichuan	China	610016
153	Chengdu Second People's Hospital	Chengdu	Sichuan	China	610017
154	Sichuan Provincial People's Hospital	Chengdu	Sichuan	China	610041
155	The West China Hospital	Chengdu	Sichuan	China	610041
156	Sichuan Mianyang 404 Hospital	Sichuan	Sichuan	China	621000
157	Tianjin Union Hospital	Tianjin	Tianjin	China	300050
158	Tianjin Chest Hospital	Tianjin	Tianjin	China	300051
159	Tianjin Union Medicine Centre	Tianjin	Tianjin	China	300121
160	Army Police's Medical College Affiliated Hospital	Tianjin	Tianjin	China	300162
161	Tianjin Third Central Hospital	Tianjin	Tianjin	China	300170
162	Tianjin First Center Hospital	Tianjin	Tianjin	China	300192
163	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin	China	300211
164	Dagang Oil-Field General Hospital	Tianjin	Tianjin	China	300280
165	The Fifth Central Hospital of Tianjin	Tianjin	Tianjin	China	300450
166	First Affiliated Hospital of the Medical College	Shihezi	Xinjiang	China	832008
167	Xin Jiang Traditional Chinese Medicine Hospital	Urumqi	Xinjiang	China	830000
168	General Hospital of Xinjiang Production and Construction Corps	Urumqi	Xinjiang	China	830002
169	The 474th Hospital of PLA	Urumqi	Xinjiang	China	830013
170	The First Teaching Hospital of Xinjiang Medical University	Urumqi	Xinjiang	China	830054
171	The First Affiliated Hospital of Kunming Medical College	Kunming	Yunnan	China	650032
172	The First People's Hospital of Yunnan Province	Kunming	Yunnan	China	650032
173	The Second Affiliated Hospital of Kunming Medical College	Kunming	Yunnan	China	650101
174	People's Hospital of Yuxi City	Yuxi	Yunnan	China	653100
175	Zhe Jiang Hospital	Hangzhou	Zhejiang	China	310013
176	Sir Run Run Shaw Hospital Affiliated With School of Medicine, Zhe Jiang University	Hangzhou	Zhejiang	China	310016
177	Prince of Wales Hospital	Hong Kong		Hong Kong