Safety and Efficacy of Valsartan vs Atenolol and Hydrochlorothiazide Combination on Blood Flow in Hypertensive Patients

A Randomized, Open-label, Multicenter, Cross-over Trial to Evaluate the Efficacy of a 20 Week Treatment of Valsartan 320 mg Versus Atenolol 100 mg in Combination With Hydrochlorothiazide on Microcirculation in Hypertensive Patients

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00396656

Enrollment

Registered

2006-11-07

Start date

2005-12-31

Completion date

2007-12-31

Last updated

2011-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypertension

Keywords

hypertension, valsartan, atenolol, hydrochlorothiazide, microcirculation, arterial compliance, pulse wave analysis

Brief summary

This study evaluated the effect of valsartan on small vessel blood flow in patients with mild-to-moderate hypertension in direct comparison to atenolol and hydrochlorothiazide.

Interventions

DRUGAtenolol

100 mg tablets orally once a day (od) in the morning.

DRUGHydrochlorothiazide (HCTZ))

12.5 or 25 mg tablets orally once a day (od) in the morning.

DRUGValsartan

80 mg, 160 mg, or 320 mg tablets orally once a day in the morning

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Caucasian; male or female outpatients and age between 40-65 years of age, inclusive. * At Visit 2 all patients must have a mean sitting diastolic blood pressure (msSBP) of ≥ 90 mmHg and \< 110 mmHg.

Exclusion criteria

* If a single reading for arterial hypertension in msSBP \> 180 mmHg or msDBP \> 110 mmHg at any visit after randomization. * Inability to discontinue all prior antihypertensive medications safely for a period of 2 weeks prior to randomization. * Known history of hypotensive symptoms or orthostatic hypotension. * Concomitant use of statins or statin intake during the four weeks prior to Visit 1. * Known Keith-Wagener grade III or IV hypertensive retinopathy. * A history of heart failure (NYHA II-IV).

Design outcomes

Primary

Measure	Time frame	Description
Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Injected Sites Compared to NaCl Injected Sites	At end of each treatment period (Week 21 and Week 43)	10 µl of acetylcholine (ACH) at 3 concentrations (10-7, 10-8, 10-9 M) was injected intra-dermally at 3 sites on the forearms. NaCl was injected at 2 sites on the forearms. Microcirculation was measured using laser doppler velocimetry before and 12 times in the 30 minutes following injection. The mean difference of the 12 post-injection measurements to the pre-injection measurement was calculated. Means for the 3 ACH and the 2 NaCl sites were calculated and compared. Microcirculation was measured in perfusion units which is an arbitrary measure specific to each laser doppler scanner.

Secondary

Measure	Time frame	Description
Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Plus L-NMMA Injected Sites Compared to NaCl Injected Sites	At end of each treatment period (Week 21 and Week 43)	10 µl of acetylcholine (ACH) at 3 concentrations (10-7, 10-8, 10-9 M) plus 10 µl L-NMMA (10-6 M) was injected intra-dermally at 3 sites on the forearms. NaCl was injected at 2 sites. Microcirculation was measured using laser doppler velocimetry before and 12 times in the 30 minutes following injection. The mean difference of the 12 post-injection measurements to the pre-injection measurement was calculated. Means for the 3 ACH and the 2 NaCl sites were calculated and compared. Microcirculation was measured in perfusion units which is an arbitrary measure specific to each laser doppler scanner.
Difference in Mean Post-treatment Microcirculation at a Sodium Nitroprusside Injected Site Compared to NaCl Injected Sites	At end of each treatment period (Week 21 and Week 43)	10 µl of sodium nitroprusside at a concentration of 10-7 M was injected intra-dermally at 1 site on the forearms. NaCl was injected at 2 sites on the forearms. Microcirculation was measured using laser doppler velocimetry before and 12 times in the 30 minutes following injection. The mean difference of the 12 post-injection measurements to the pre-injection measurement was calculated. A mean for the 2 NaCl sites was calculated and compared to the sodium nitroprusside mean. Microcirculation was measured in perfusion units which is an arbitrary measure specific to each laser doppler scanner.
Mean Post-treatment Microcirculation at NaCl Injected Sites	At end of each treatment period (Week 21 and Week 43)	10 µl of NaCl was injected intra-dermally at 2 sites on the forearms. Microcirculation was measured using laser doppler velocimetry before and 12 times in the 30 minutes following injection. The mean difference of the 12 post-injection measurements to the pre-injection measurement was calculated. A mean for the 2 NaCl sites was calculated. Microcirculation was measured in perfusion units which is an arbitrary measure specific to each laser doppler scanner.
Arterial Pressure Waveform Augmentation Index at the End of Treatment	At end of each treatment period (Week 21 and Week 43)	Using applanation tonometry, the arterial pulse form measured at the wrist was analyzed using computerized pulse wave analysis. The arterial pressure waveform has two components; the first is the forward traveling wave when the left ventricle contracts and the second is the reflected wave returning from the periphery. The augmentation index is the ratio of the first and second systolic peaks and is used as a surrogate measure of arterial stiffness.
Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment	At end of each treatment period (Week 21 and Week 43)	Using applanation tonometry, the arterial pulse form measured at the wrist was analyzed using computerized pulse wave analysis. The arterial pressure waveform has two components; the first is the forward traveling wave when the left ventricle contracts and the second is the reflected wave returning from the periphery. Pulse wave velocity is the speed of the forward traveling wave and can be used as a measure of arterial stiffness since the more rigid the wall of the artery, the faster the wave moves.

Countries

Germany, Switzerland

Participant flow

Participants by arm

Arm	Count
Entire Study Population Includes patients that received valsartan followed by atenolol + hydrochlorothiazide and patients that received atenolol + hydrochlorothiazide followed by valsartan.	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Treatment Period	Withdrawal by Subject	0	2
Second Treatment Period	Adverse Event	0	1

Baseline characteristics

Characteristic	Entire Study Population
Age Continuous	52.3 years STANDARD_DEVIATION 7.2
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	19 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	16 / 28	12 / 30
serious Total, serious adverse events	0 / 28	1 / 30

Outcome results

Primary

Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Injected Sites Compared to NaCl Injected Sites

10 µl of acetylcholine (ACH) at 3 concentrations (10-7, 10-8, 10-9 M) was injected intra-dermally at 3 sites on the forearms. NaCl was injected at 2 sites on the forearms. Microcirculation was measured using laser doppler velocimetry before and 12 times in the 30 minutes following injection. The mean difference of the 12 post-injection measurements to the pre-injection measurement was calculated. Means for the 3 ACH and the 2 NaCl sites were calculated and compared. Microcirculation was measured in perfusion units which is an arbitrary measure specific to each laser doppler scanner.