Efficacy and Safety of Valsartan Versus Amlodipine in Postmenopausal Women With Hypertension

Study Overview
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Brief Summary
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The purpose of this study is compare treatment with valsartan with the possible addition of a diuretic, hydrochlorothiazide, on high blood pressure with the drug amlodipine with the possible addition of a diuretic, hydrochlorothiazide. In particular, the effect of treatment on the stiffness of the blood vessels will be studied.

Official Title
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A Randomized, Double-blind, Parallel Group, Active-controlled, 38-week Study to Evaluate the Efficacy of Valsartan Versus Amlodipine on the Arterial Properties of Postmenopausal Women With Mild to Moderate Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Valsartan 320 mg
* Drug: Amlodipine 10 mg
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women Mild to moderate hypertension Statin therapy or LDL≤ 4.1 mmol/L Exclusion Criteria: Severe hypertension LDL > 4.1 mmol/L if not taking anti-hyperlipidemic medication Certain hormonal therapy History of stroke, myocardial infarction, heart failure, chest pain, abnormal heart rhythm Liver, kidney, or pancreas disease Diabetes Raynaud's disease or any other significant peripheral vascular disease Allergy to certain medications used to treat high blood pressure Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan 320 mg<br> | Drug: Valsartan 320 mg<br>* Patients received 160 mg valsartan for 4 weeks. Patients were then up-titrated to receive either 320 mg valsartan for the following 8 weeks.<br>Drug: Hydrochlorothiazide<br>* At Week 12, patients who did not meet target Blood Pressure for both Systolic Blood Pressure < 140 mmHg and Diastolic Blood Pressure < 90 mmHg were eligible to receive 12.5 mg open-label Hydrochlorothiazide for the following 26 weeks.<br>|
| Experimental: Amlodipine 10 mg<br> | Drug: Amlodipine 10 mg<br>* Patients received 5 mg amlodipine for four weeks. Patients were then up-titrated to receive 10 mg amlodipine for the following 8 weeks.<br>Drug: Hydrochlorothiazide<br>* At Week 12, patients who did not meet target Blood Pressure for both Systolic Blood Pressure < 140 mmHg and Diastolic Blood Pressure < 90 mmHg were eligible to receive 12.5 mg open-label Hydrochlorothiazide for the following 26 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 38 in the Carotid-femoral Pulse Wave Velocity (PWV) | PWV was determined from transcutaneous Doppler flow recordings and the foot-to-foot method triggered by the simultaneous ECG. Two simultaneous Doppler flow tracings were taken at the left common carotid and the right femoral artery in the groin with a linear array probe. The time delay (t) was measured between R wave of the ECG and the base of the flow waves recorded at these points, and averaged over 10 beats. The distance (D) traveled by the pulse wave was measured over body surface as the distance from the suprasternal notch to the carotid artery. PWV was calculated as PWV=D/t. | Baseline and Week 38 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Week 12 | Cutaneous blood flow was continuously recorded by a laser Doppler flowmeter. The laser Doppler flow probe was applied on the volar part of the right forearm with a plastic holder 10 cm proximal to the wrist. All measurements were made with a pressure cuff on the arm and inflated 20 mmHg above systolic BP and maintained for 2 min then rapidly deflated. All measurements were made in a quiet room with a patient in the supine position. The maximal reactive hyperemia was measured after cuff deflation, which allows measurement of the right forearm postischemic skin reactive hyperemia (SRH). | Baseline and Week 12 | 
| Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Endpoint (Week 38) | Cutaneous blood flow was continuously recorded by a laser Doppler flowmeter. The laser Doppler flow probe was applied on the volar part of the right forearm with a plastic holder 10 cm proximal to the wrist. All measurements were made with a pressure cuff on the arm and inflated 20 mmHg above systolic BP and maintained for 2 min then rapidly deflated. All measurements were made in a quiet room with a patient in the supine position. The maximal reactive hyperemia was measured after cuff deflation, which allows measurement of the right forearm postischemic skin reactive hyperemia (SRH). | Week 38 | 
| Change From Baseline for Endothelial Function Measured by Brachial Artery Flow-mediated Vasodilatation (FMD) Using the Brachial Artery Reactivity Test (BART) at Week 12 | Endothelial function will be assessed using high-resolution duplex ultrasound with wall tracking to measure FMD of the brachial artery during reactive hyperemia. FMD of the brachial artery in response to reactive hyperemia in the distal forearm (and glyceryl trinitrate as a non-endothelium dependent control) will be measured from B-mode ultrasound images using a standard 7 MHz linear array transducer and HDI 5000 system with edge detection. | Baseline and Week 12 | 
| Change From Baseline for Endothelial Function Measured by Brachial Artery Flow-mediated Vasodilatation (FMD) Using the Brachial Artery Reactivity Test (BART) at End-point (Week 38) | Endothelial function will be assessed using high-resolution duplex ultrasound with wall tracking to measure FMD of the brachial artery during reactive hyperemia. FMD of the brachial artery in response to reactive hyperemia in the distal forearm (and glyceryl trinitrate as a non-endothelium dependent control) will be measured from B-mode ultrasound images using a standard 7 MHz linear array transducer and HDI 5000 system with edge detection. | Baseline and Week 38 | 
| Changes in Mean Left Carotid Distensibility at Week 12 | For carotid distensibility, the left and right bulbs and common carotid arteries are measured using tissue Doppler imaging with the linear array probe. Absolute diameter and diameter changes over the cardiac cycles will be recorded. Distensibility of each bulb will be calculated for three consecutive heart cycles and averaged and corrected for blood pressure. | Baseline and Week 12 | 
| Changes in Mean Left Carotid Distensibility at Week 38 | For carotid distensibility, the left and right bulbs and common carotid arteries are measured using tissue Doppler imaging with the linear array probe. Absolute diameter and diameter changes over the cardiac cycles will be recorded. Distensibility of each bulb will be calculated for three consecutive heart cycles and averaged and corrected for blood pressure. | Baseline and Week 38 | 
| Changes in Mean Right Carotid Distensibility at Week 12 | For carotid distensibility, the left and right bulbs and common carotid arteries are measured using tissue Doppler imaging with the linear array probe. Absolute diameter and diameter changes over the cardiac cycles will be recorded. Distensibility of each bulb will be calculated for three consecutive heart cycles and averaged and corrected for blood pressure. | Baseline and Week 12 | 
| Changes in Mean Right Carotid Distensibility at Week 38 | For carotid distensibility, the left and right bulbs and common carotid arteries are measured using tissue Doppler imaging with the linear array probe. Absolute diameter and diameter changes over the cardiac cycles will be recorded. Distensibility of each bulb will be calculated for three consecutive heart cycles and averaged and corrected for blood pressure. | Baseline and Week 38 | 
| Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 12 | The calculation of spontaneous baroflex sensitivity was obtained by the sequence method. Baroflex sequences are defined by at least three consecutive beats in which the systolic blood pressure and the RR interval of the following beat either both increased or decreased. The slope of each individual sequence is computed and the mean slope is determined as the average of all slopes within a given period of time and taken as the gain of the cardiac baroflex (BRSs). | Baseline and Week 12 | 
| Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 38 | The calculation of spontaneous baroflex sensitivity was obtained by the sequence method. Baroflex sequences are defined by at least three consecutive beats in which the systolic blood pressure and the RR interval of the following beat either both increased or decreased. The slope of each individual sequence is computed and the mean slope is determined as the average of all slopes within a given period of time and taken as the gain of the cardiac baroflex (BRSs). | Baseline and Week 38 | 
| Change in Left Ventricular Mass Index (LVMI) and Diastolic Function Using Echocardiography From Baseline to Week 38 |  | Baseline and Week 38 | 
| Changes in Central Blood Pressure, Evaluated by Applanation Tonometry From Baseline at Weeks 12 and 38 | Central Blood Pressure was measured via applanation tonometry recordings of the common carotid artery and from brachial oscillometric recordings. The Simultaneously obtained carotid artery pressure and standard brachial artery blood pressure are computed to obtain the central systolic pressure. | Baseline, Week 12 and Week 38 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, postmenopausal, valsartan, amlodipine, hydrochlorothiazide