Trial Outcomes & Findings for Efficacy and Safety of Valsartan Versus Amlodipine in Postmenopausal Women With Hypertension (NCT NCT00171054)

NCT ID: NCT00171054

Last Updated: 2011-06-06

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 125 participants
• Primary outcome timeframe: Baseline and Week 38
• Results posted on: 2011-06-06

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	63	62
Overall Study COMPLETED	53	50
Overall Study NOT COMPLETED	10	12

Reasons for withdrawal

Measure	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.	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.
Overall Study Protocol Violation	1	2
Overall Study Patient withdrew consent	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Adverse Event	8	8
Overall Study Condition no longer required study drug	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Valsartan 320 mg n=63 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.	Amlodipine 10 mg n=62 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.	Total n=125 Participants Total of all reporting groups
Age Continuous	62.3 years STANDARD_DEVIATION 5.76 • n=5 Participants	60.4 years STANDARD_DEVIATION 5.08 • n=7 Participants	61.4 years STANDARD_DEVIATION 5.50 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	62 Participants n=7 Participants	125 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 38

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=56 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Change From Baseline to Week 38 in the Carotid-femoral Pulse Wave Velocity (PWV)	-1.9 m/s Standard Error 0.29	-1.7 m/s Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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)

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).

Outcome measures

Measure	Valsartan 320 mg n=54 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Week 12	25.4 Perfusion units Standard Error 14.88	-105.6 Perfusion units Standard Error 15.31

SECONDARY outcome

Timeframe: Week 38

Population: 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)

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).

Outcome measures

Measure	Valsartan 320 mg n=55 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Change From Baseline in Post-ischemic Forearm Skin Reactive Hyperemia at Endpoint (Week 38)	-9.7 Perfusion units Standard Error 13.73	-94.6 Perfusion units Standard Error 14.20

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=56 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.	Amlodipine 10 mg n=49 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Change From Baseline for Endothelial Function Measured by Brachial Artery Flow-mediated Vasodilatation (FMD) Using the Brachial Artery Reactivity Test (BART) at Week 12	-8.7 percent Standard Error 0.35	-8.6 percent Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline and Week 38

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=56 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.	Amlodipine 10 mg n=51 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at 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)	-8.1 percent Standard Error 0.53	-8.2 percent Standard Error 0.56

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=54 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.	Amlodipine 10 mg n=51 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Mean Left Carotid Distensibility at Week 12	0.0 percent Standard Error 0.14	0.0 percent Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and Week 38

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=54 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Mean Left Carotid Distensibility at Week 38	0.0 percent Standard Error 0.16	0.1 percent Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=54 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.	Amlodipine 10 mg n=52 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Mean Right Carotid Distensibility at Week 12	-0.4 percent Standard Error 0.16	0.1 percent Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline and Week 38

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=54 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Mean Right Carotid Distensibility at Week 38	-0.2 percent Standard Error 0.17	0.0 percent Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: 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)

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).

Outcome measures

Measure	Valsartan 320 mg n=55 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.	Amlodipine 10 mg n=52 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 12	1.5 EP Standard Error 1.71	-1.5 EP Standard Error 1.78

SECONDARY outcome

Timeframe: Baseline and Week 38

Population: 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)

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).

Outcome measures

Measure	Valsartan 320 mg n=56 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.	Amlodipine 10 mg n=52 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Baroreflex Sensitivity as it Relates to Changes in Carotid Distensibility From Baseline to Week 38	-2.0 EP Standard Error 1.38	0.1 EP Standard Error 1.44

SECONDARY outcome

Timeframe: Baseline and Week 38

Population: 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)

Outcome measures

Measure	Valsartan 320 mg n=19 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.	Amlodipine 10 mg n=22 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Change in Left Ventricular Mass Index (LVMI) and Diastolic Function Using Echocardiography From Baseline to Week 38	-4.8 percent Standard Error 2.43	-6.2 percent Standard Error 2.13

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 38

Population: 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)

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.

Outcome measures

Measure	Valsartan 320 mg n=56 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.	Amlodipine 10 mg n=53 Participants Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Changes in Central Blood Pressure, Evaluated by Applanation Tonometry From Baseline at Weeks 12 and 38 Week 12	-9.1 mm Hg Standard Error 1.06	-14.2 mm Hg Standard Error 1.10
Changes in Central Blood Pressure, Evaluated by Applanation Tonometry From Baseline at Weeks 12 and 38 Week 36	-11.1 mm Hg Standard Error 1.07	-13.9 mm Hg Standard Error 1.12

Adverse Events

Valsartan 320 mg

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Amlodipine 10 mg

Serious events: 2 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	Valsartan 320 mg n=63 participants at risk 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.	Amlodipine 10 mg n=62 participants at risk Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Eye disorders Diplopia	0.00% 0/63	1.6% 1/62
Nervous system disorders Cerebrovascular accident	0.00% 0/63	1.6% 1/62
Nervous system disorders Syncope	1.6% 1/63	0.00% 0/62
Nervous system disorders Transient ischaemic attack	1.6% 1/63	0.00% 0/62
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/63	1.6% 1/62

Other adverse events

Measure	Valsartan 320 mg n=63 participants at risk 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.	Amlodipine 10 mg n=62 participants at risk Amlodipine, orally administered, was provided as 5 mg capsules. Open-label HCTZ 12.5 mg (orally administered) was electively prescribed at week 12.
Ear and labyrinth disorders Vertigo	6.3% 4/63	3.2% 2/62
General disorders Asthenia	7.9% 5/63	3.2% 2/62
General disorders Fatigue	0.00% 0/63	6.5% 4/62
General disorders Oedema peripheral	14.3% 9/63	77.4% 48/62
Infections and infestations Bronchitis	12.7% 8/63	0.00% 0/62
Musculoskeletal and connective tissue disorders Muscle spasms	3.2% 2/63	6.5% 4/62
Musculoskeletal and connective tissue disorders Pain in extremity	1.6% 1/63	6.5% 4/62
Nervous system disorders Headache	9.5% 6/63	8.1% 5/62
Psychiatric disorders Insomnia	6.3% 4/63	1.6% 1/62
Vascular disorders Hypotension	7.9% 5/63	0.00% 0/62

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER