Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr J.J. Wiersma


Contact details

Academic Medical Centre
Department of Cardiology
Meibergdreef 9
1105 AZ
+31 (0)20 5662749

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title



Study hypothesis

To determine whether a strategy of invasive treatment (relative to continued medical treatment) of patients with type 2 diabetes mellitus, mild symptoms of stable angina pectoris, and documented myocardial ischemia lead to a decrease in cardiac complications

Ethics approval

Received from local medical ethics committee

Study design

Multicentre randomised open label active controlled parallel group trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Diabetes Mellitus type II (DM type II), Coronary artery disease


Patients that qualify for admission in the randomised trial are randomly assigned to one of the following treatment strategies:
1. Invasive treatment
2. Continued medical treatment

Invasive treatment:
Patients undergo coronary angiography as soon as possible after randomisation. Angiography can be performed at either the referring center or the intervention center. Coronary angiography is performed according to current practice guidelines by experienced operators. The sheath and catheter size should not exceed 6 F.
All patients follow the routine assessment in the regular heart team conferences, in which the referring cardiologist, the heart surgeon, and the intervention cardiologist take decisions about the type of revascularisation. The Dutch Guidelines for revascularisation are followed except for the required intensity of the anginal complaints.
PTCA procedures are performed under routine protocols of the participating catheterisation laboratories. The aim is to treat all culprit lesions i.e. those lesions that are associated with significant deficits on the myocardial perfusion scintigram. All lesions are preferably treated with a paclitaxel-coated stent, unless contra-indicated or not available. Blood samples for the measurement of concentrations of CK and CK-MB are taken at 6, 12, 18, and 24 hours after the end of a percutaneous procedure. These concentrations are measured at the local laboratories.
Treatment with GP IIb/IIIa receptor inhibitors is recommended. Clopidogrel is started before the PTCA and continued until at least 1 month after stenting and until 6 months after stenting when a drug-eluting stent is placed.
Bypass surgery is performed under the routine protocols of the participating hospitals. The aim is to achieve complete revascularisation.
After a revascularisation procedure, the antianginal medication is reduced as much as possible.

Continued medical treatment:
Anti-anginal medication: Beta-blockers, calcium antagonists, oral nitrates may be given as clinically needed.
Acetyl salicylic acid: Acetyl salicylic acid at a dose of at least 75 mg/24 hours is given to all patients at least until the end of follow-up (unless contraindicated).
Clopidogrel: Clopidogrel is given to patients that undergo a percutaneous intervention in combination with stent placement. Clopidogrel is given at a starting dose of 300 mg immediately before stent placement, followed by 75 mg daily for 3 months. Moreover, clopidogrel at a dose of 75 mg/24 hours may also be given to patients with a contra-indication for acetyl salicylic acid.
Statins: Aggressive lipid lowering therapy should be started in all patients as soon as possible after informed consent has been obtained. Further treatment of dislipidemia is according to present consensus guidelines.
ACE-inhibitors: ACE-inhibitors: Treatment with ramipril is started as soon as possible after informed consent has been obtained. Ramipril is started at a dose of 2.5 mg/24 hours for one week, followed 5.0 mg/24 hours for three weeks. After one month, the treatment is continued at a dose of 10 mg/ 24 hours.
If deemed necessary by the treating physician, another ACE inhibitor or an AT-II receptor antagonist may be given.
Other antihypertensive drugs: Hypertension is treated according to the current guidelines, which aim at a systolic blood pressure of <140 mmHg and a diastolic blood pressure of <85 mmHg.
Other drugs: Other drugs be given when indicated; their use is recorded.

Intervention type



Not Specified

Drug names

Primary outcome measure

One or more of the following complications within the duration of follow-up:
1. All-cause mortality
2. Non-fatal myocardial infarction
3. Hospital admission for acute coronary syndrome

Secondary outcome measures

Each of the above components of the composite endpoint:
1. Cardiac mortality
2. Newly developed diabetic morbidity (diabetic retinopathy, diabetic nephropathy, and changes in blood glucose regulation) documented in routine clinical practice
3. Functional status at one and two years
4. Quality of life

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. A history of diabetes mellitus type 2, evidenced by either of the following
1.1 Treatment with oral antidiabetic medication
1.2 Treatment with insulin after a period of treatment with oral antidiabetic medication
1.3 Treatment with insulin, started after the 50th year
1.4 A fasting plasma glucose concentration of at least 7.0 mmol/l or a non-fasting glucose concentration of at least 11.0 mmol/l, in two samples taken on separate days
2. Stable mild complaints of angina pectoris (Canadian Cardiovascular Society class I or II, on medical treatment)

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Younger than 30 years of age
2. Previous myocardial infarction and/or acute coronary syndrome in the previous two months
3. Unstable angina (any category in Braunwald's classification) in the previous two months
4. Previous percutaneous intervention in the previous six months
5. Serious complaints of effort angina pectoris (CCS class III or IV)
6. Known coronary anatomy unsuited for coronary revascularization
7. An ejection fraction of less than 35%, measured by any technique
8. Contra-indication for bypass surgery (i.e. co-morbidity)
9. History of a hemorrhagic stroke at any time, or stroke or transient ischemic accident (TIA) of any etiology within 30 days of randomization
10. History of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days of randomization
11. Known platelet count of <100,000/mm3
12. Severe hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure over 100 mmHg, after treatment)
13. Major surgery within 6 weeks prior to randomization
14. Congenital heart disease
15. Apparent cardiomyopathy
16. Severe valvular heart disease
17. Serious bronchial asthma
18. Malignancies or other diseases with a limited life expectancy
19. Serious kidney failure (plasma creatinin level >250 µmol/l)
20. Body-weight >120 kg
21. Co-existent condition associated with a limited life expectancy
22. Previous participation in this study or any other trial within the previous 30 days
23. Circumstances that prevent follow-up (no permanent home or address, transient etc.)
24. Pregnant women or women of child bearing potential who do not use adequate contraception
25. Familial hypercholesterolemia or an LDL cholesterol concentration over 55 mmol/l (after treatment)

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Academic Medical Centre,
1105 AZ

Sponsor information


Academic Medical Centre (AMC) (Netherlands)

Sponsor details

Meibergdreef 9
1105 AZ

Sponsor type




Funder type

Research organisation

Funder name

Netherlands Organisation for Health Research and Development (ZonMw)

Alternative name(s)

Netherlands Organisation for Health Research and Development

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit



Funder name

Dutch Heart Foundation (Netherlands)

Alternative name(s)

Dutch Heart Foundation

Funding Body Type

private sector organisation

Funding Body Subtype




Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2009 results in

Publication citations

  1. Results

    Wiersma JJ, Verberne HJ, ten Holt WL, Radder IM, Dijksman LM, van Eck-Smit BL, Trip MD, Tijssen JG, Piek JJ, Prognostic value of myocardial perfusion scintigraphy in type 2 diabetic patients with mild, stable angina pectoris., J Nucl Cardiol, 16, 4, 524-532, doi: 10.1007/s12350-009-9111-z.

Additional files

Editorial Notes