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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Valsartan 320 mg | Experimental |
| |
| Amlodipine 10 mg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valsartan 320 mg | Drug | Patients received 160 mg valsartan for 4 weeks. Patients were then up-titrated to receive either 320 mg valsartan for the following 8 weeks. |
|
| 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 |
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Pharmaceuticals | Basel | Switzerland |
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| ID | Title | Description |
|---|---|---|
| FG000 | Valsartan 320 mg | Double-blind study medication consisted of valsartan 160 mg capsules for oral administration. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
| FG001 | Amlodipine 10 mg | Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Valsartan 320 mg | Double-blind study medication consisted of valsartan 160 mg capsules for oral administration. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
| BG001 | Amlodipine 10 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | m/s | Baseline and Week 38 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Valsartan 320 mg | Double-blind study medication consisted of valsartan 160 mg capsules for oral administration. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diplopia | Eye disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068756 | Valsartan |
| D017311 | Amlodipine |
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D013777 | Tetrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Amlodipine 10 mg | Drug | Patients received 5 mg amlodipine for four weeks. Patients were then up-titrated to receive 10 mg amlodipine for the following 8 weeks. |
|
| Hydrochlorothiazide | Drug | 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. |
|
| 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 |
| Lost to Follow-up |
|
| Adverse Event |
|
| Condition no longer required study drug |
|
Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Double-blind study medication consisted of valsartan 160 mg capsules for oral administration. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
| OG001 | Amlodipine 10 mg | Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. |
|
|
| Secondary | 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). | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | Perfusion units | Baseline and Week 12 |
|
|
|
| Secondary | 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). | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | Perfusion units | Week 38 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 12 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 38 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 12 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 38 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 12 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 38 |
|
|
|
| Secondary | 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). | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | EP | Baseline and Week 12 |
|
|
|
| Secondary | 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). | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | EP | Baseline and Week 38 |
|
|
|
| Secondary | Change in Left Ventricular Mass Index (LVMI) and Diastolic Function Using Echocardiography From Baseline to Week 38 | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | percent | Baseline and Week 38 |
|
|
|
| Secondary | 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. | Intent-to-treat. The intent to treat population is defined as those who provide a baseline measure and at least one post-baseline measurement (not necessarily an endpoint measure) | Posted | Least Squares Mean | Standard Error | mm Hg | Baseline, Week 12 and Week 38 |
|
|
|
| 2 |
| 63 |
| 35 |
| 63 |
| EG001 | Amlodipine 10 mg | Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12. | 2 | 62 | 51 | 62 |
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D014633 |
| Valine |
| D000597 | Amino Acids, Branched-Chain |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |