Study on the vascular effects of ACE-I + CA-antagonist (Enalapril + Lercanidipine) versus ACE-I + diuretic (Enalapril + hydrochlorothiazidE) combinations in hypertensive patients with metabolic syndrome not sufficiently controlled by ACE-I monotherapy

INTERVENTION: Pharmaceutical Form: Tablet INN or Proposed INN: Enalapril Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical Form: Tablet INN or Proposed INN: Lercanidipine Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical Form: Tablet INN or Proposed INN: Thiazides, plain Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 12.5‐ CONDITION: hypertensive patients of either sex aged 40‐69 years ; MedDRA version: 9.1 Level: HLGT Classification code 10057166 ; MedDRA version: 9.1 Level: SOC Classification code 10047065 ; MedDRA version: 9.1 Level: SOC Classification code 10047065 ; MedDRA version: 9.1 Level: SOC Classification code 10047065 PRIMARY OUTCOME: Main Objective: Primary objective The primary objective of the study is to assess the effects of a 24‐week treatment period with the two investigational medicinal products (IMPs) combinations on arterial stiffness (aortic pulse wave velocity, PWV). Primary end point(s): The primary efficacy variable of the study is the change from baseline to the end of treatment of the aortic PWV (m/sec) measured at the end of the 24 weeks of treatment. Secondary Objective: Secondary objectives The secondary objectives of the study are to assess the effects of a 24‐week treatment period with the two IMPs combinations on the following parameters: Parameters of pressure wave reflection (augmentation index ‐ AIx) and central arterial pressure; Endothelial function: flow mediated dilation (FMD) of brachial artery; Sitting blood pressure and heart rate measured at clinics; 24‐hour blood pressure monitoring (ABPM); Adverse events and adverse drug reactions: Metabolic effects (lipid and glucose profile, insulin‐resistance); ECG parameters; Routine laboratory parameters (haematology, blood chemistry and urinalysis). INCLUSION CRITERIA: Patients will be enrolled at Visit 1 into the run‐in period if they meet all the following criteria: 1. Men or post‐menopausal women that express their willing to participate in the study by signing the informed consent; 2. Subjects aged 40‐69 years (inclusive); 3. Medical history of arterial hypertension not controlled with ACE‐inhibitors given as monotherapy. 4. Subjects satisfying any 3 of the following 5 criteria of metabolic syndrome, defined according to the criteria of the American Heart Association (Grundy et al, 2005): Elevated waist circumference (≥ 102 cm in men and ≥ 88 cm in women); Elevated triglycerides (≥ 150 mg/dl): Reduced HDL cholesterol (< 40 mg/dl in men and < 50 mg/dl in women); Elevated blood pressure (SBP ≥ 130 mmHg or DBP ≥ 85 mmHg); Elevated fasting plasma glucose (FPG ≥ 100 mg/dl) or drug treatment for elevated glucose levels; 5. Patient?s co‐operative attitud