The purpose of this study is to evaluate the effect of high dose Renin-Angiotensin System (RAS)-antagonists and beta-blocker treatment for the primary prevention of cardiac events in a population of patients with Type 2 diabetes mellitus (T2DM) with no evidence of a preexisting cardiac disease.
Conditions
Sponsors
Medizinische Universität Wien
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Type-2 diabetes mellitus for at least six months, 2) = 18 years of age, men or female, 3) Written informed consent to participate in the study and ability to comply with all requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 1) History of hypersensitivity to any of the drugs investigated as well as known or suspected contraindications to the study drugs or previous history of intolerance to high dose of RAAS-antagonists or beta-blocker in the absence of any other blood pressure lowering drugs. 2) Patients already receiving a maximum dose of RAAS-antagonists or beta-blocker. 3) Creatinine > 2.5mg/dl. 4) Symptomatic hypotension and/or systolic blood pressure (SBP) grades I. 8) Coronary artery disease, defined by a history of myocardial infarction, known coronary stenosis > 70% detected either by angiography or by CT-scan, significant defects in myocardial scintigraphy or positive stress-test echocardiography. 9) A disease other than diabetes lowering the patient’s life expectancy to less than two years. 10) Chronic infections or malignancies. 11) Systemic treatment with corticosteroids. 12) Renal replacement therapy. 13) Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (if accepted by local regulatory authority and ethics committee). Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. 14) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test ( > 5mIU/ml). 15) History of noncompliance to medical regimes and patients who are considered potentially unreliable. 16) Current double blind treatment in diabetic trials. 17) Participation in an investigational drug study at the time of enrollment or within the past 90 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Superiority of high dose treatment with RAS-antagonists and beta-blockers compared to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients with a NT-proBNP > 125pg/ml. Co-primary objective: Superiority of high dose treatment with RAS-antagonists and beta-blockers compared to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients in the whole population ;Secondary Objective: Secondary objective: Dependency of treatment efficacy (reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients) on the NT-proBNP concentration (interaction effect between NT-proBNP concentrations and treatment). ;Primary end point(s): The primary endpoint are unplanned hospitalization or death due to a cardiac event in T2DM patients with a NT-proBNP > 125pg/ml. The co-primary endpoint is whether high dose treatment with RAS-antagonists and beta-blockers is superior to conventional therapy regarding the reduction of unplanned hospitalization or death due to a cardiac event in T2DM patients in the whole population;Timepoint(s) of evaluation of this end point: The primary endpoints will be evaluated in the 2-years study period and will be further followed-up by telephone calls or registers. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints is an interaction effect between NT-proBNP concentrations and treatment efficacy.;Timepoint(s) of evaluation of this end point: The primary endpoints will be evaluated in the 2-years study period and will be further followed-up by telephone calls or registers. | — |
Countries
Austria, Croatia, Ireland, Netherlands, New Zealand, Slovenia, Spain, United Kingdom, United States
Contacts
Public ContactPrincipal Investigator
Medizinische Universität Wien
Outcome results
None listed