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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00171054
First received: September 10, 2005
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Valsartan 320 mg
Drug: Amlodipine 10 mg
Drug: Hydrochlorothiazide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline to Week 38 in the Carotid-femoral Pulse Wave Velocity (PWV) [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Endpoint (Week 38) [ Time Frame: Week 38 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline for Endothelial Function Measured by Brachial Artery Flow-mediated Vasodilatation (FMD) Using the Brachial Artery Reactivity Test (BART) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
    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.

  • Changes in Mean Left Carotid Distensibility at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Changes in Mean Left Carotid Distensibility at Week 38 [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
    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.

  • Changes in Mean Right Carotid Distensibility at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Changes in Mean Right Carotid Distensibility at Week 38 [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
    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.

  • Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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).

  • Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 38 [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
    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).

  • Change in Left Ventricular Mass Index (LVMI) and Diastolic Function Using Echocardiography From Baseline to Week 38 [ Time Frame: Baseline and Week 38 ] [ Designated as safety issue: No ]
  • Changes in Central Blood Pressure, Evaluated by Applanation Tonometry From Baseline at Weeks 12 and 38 [ Time Frame: Baseline, Week 12 and Week 38 ] [ Designated as safety issue: No ]
    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.


Enrollment: 125
Study Start Date: September 2003
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Valsartan 320 mg Drug: Valsartan 320 mg
Patients received 160 mg valsartan for 4 weeks. Patients were then up-titrated to receive either 320 mg valsartan for the following 8 weeks.
Drug: Hydrochlorothiazide
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.
Experimental: Amlodipine 10 mg Drug: Amlodipine 10 mg
Patients received 5 mg amlodipine for four weeks. Patients were then up-titrated to receive 10 mg amlodipine for the following 8 weeks.
Drug: Hydrochlorothiazide
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.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Female
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00171054

Locations
Switzerland
Novartis Pharmaceuticals
Basel, Switzerland
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00171054     History of Changes
Other Study ID Numbers: CVAL489A2418
Study First Received: September 10, 2005
Results First Received: December 21, 2010
Last Updated: June 2, 2011
Health Authority: Switzerland: Swissmedic

Keywords provided by Novartis:
hypertension
postmenopausal
valsartan
amlodipine
hydrochlorothiazide

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Valsartan
Amlodipine
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Calcium Channel Blockers
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 22, 2014