Comparison Between Losartan and Benazepril in Diabetic Hypertensive Patients Not Controlled by Amlodipine

Study Overview
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Brief Summary
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The purpose of this study is to compare losartan and benazepril in diabetic patients whose high blood pressure is not controlled by amlodipine and its relationship to statin current use.

Detailed Description
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Hypertension and diabetes mellitus are important risk factors for cardiovascular morbidity and mortality. Endothelial dysfunction and vascular rigidity are two pathophysiological mechanisms that may explain this relationship. Recent publications showed that both ACEi (angiotensin-converting enzyme inhibitor-induced) and ARB (angiotensin receptor blocker) were capable of improving vascular stiffness and endothelial function, and that these effects occurred despite blood pressure reduction. This study main objective is to assess if ARB (losartan) effects are different from ACEi (benazepril) in endothelial function in patients with diabetes mellitus type 2 and blood pressure not controlled by amlodipine and its relationship to statin current use. Secondary analysis of vascular stiffness will be measured by pulse wave velocity and augmentation index. Echocardiographic parameters, such as indexes of diastolic function, will also be measured.

Official Title
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Comparison Between Losartan and Benazepril in Diabetic Hypertensive Patients With Blood Pressure Not Controlled by Amlodipine: Effects on Echocardiographic Parameters, Vascular Stiffness and Endothelial Function.

Conditions
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Hypertension, Diabetes Mellitus

Intervention / Treatment
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* Drug: Benazepril
* Drug: Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatorial patients with age between 40 and 70 years-old. Systemic arterial hypertension previously diagnosed and in use of two or less anti-hypertensive drugs in the preceding 4 weeks. Type 2 diabetes mellitus in use of oral medication that were not changed in the preceding 4 weeks. Glycated hemoglobin A1c less than 9.0%. Accepted the consent form. Exclusion Criteria: Office systolic blood pressure equal or more than 180 mmHg, with or without treatment Office diastolic blood pressure equal or more than 110 mmHg, with or without treatment Evidences of a secondary cause for hypertension Glycated hemoglobin A1c > 9.0% Insulin therapy Chronic kidney disease stage 4 or 5 or in dialysis Advanced target organ lesion, obtained by history or additional exams, and defined by: previous myocardial infarction, heart failure with ejection fraction less than 40%, cerebral vascular accident (ischemic or hemorrhagic), peripheral vascular disease (claudication or doppler with obstruction > 50% of vascular lumen), retinopathy with visual loss, symptomatic neuropathy. Cardiac arrhythmias, except for ectopic beats Any clinical or disabling condition that, in the opinion of the investigators, may confound or prejudice study results. Severe mitral regurgitation. Women in fertile age without contraceptive methods in use. Breastfeeding women.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Losartan<br>This group will receive 100 mg of losartan per day. Amlodipine will be maintained. | Drug: Losartan<br>* Patients in this group will receive 100 mg of losartan per day, orally, during 12 weeks.<br>* Other names: 0006-0951-54;|
| Active Comparator: Benazepril<br>This group will receive 20 mg of benazepril per day. Amlodipine will be maintained. | Drug: Benazepril<br>* Patients in this group will receive 20 mg of benazepril per day, orally, during 12 weeks.<br>* Other names: 0078-0447-05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | Access endothelial function by brachial flow-mediated vasodilation (FMD) and compare it between groups (losartan and benazepril) and its relationship to current statin use. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Stiffness | Access vascular stiffness by pulse wave velocity and compare it between groups (losartan and benazepril). | 12 weeks. | 
| Systolic Blood Pressure | Compare both groups effects on systolic blood pressure. | 12 weeks | 
| Diastolic Blood Pressure | Compare both group effects on diastolic blood pressure. | 12 weeks | 
| Vascular Stiffness by Augmentation Index | Estimate vascular stiffness by measuring augmentation index and compare it between losartan and benazepril groups. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Diabetes Mellitus, Vascular stiffness, Endothelial function