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Safety and Efficacy of Valsartan vs Atenolol and Hydrochlorothiazide Combination on Blood Flow in Hypertensive Patients
This study has been completed.

First Received on November 6, 2006.   Last Updated on May 5, 2011   History of Changes
Sponsor: Novartis
Information provided by: Novartis
ClinicalTrials.gov Identifier: NCT00396656
  Purpose

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.


Condition Intervention Phase
Hypertension
 Drug: Atenolol
Drug: Hydrochlorothiazide (HCTZ))
Drug: Valsartan
 Phase III

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure
Drug Information available for: Hydrochlorothiazide Atenolol Valsartan
U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Injected Sites Compared to NaCl Injected Sites [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Plus L-NMMA Injected Sites Compared to NaCl Injected Sites [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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 [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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 [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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 [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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 [ Time Frame: At end of each treatment period (Week 21 and Week 43) ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: December 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

After a 2-week washout period, patients were treated with valsartan for 20 weeks followed by one week in which it was tapered off. Patients received valsartan 160 mg for 4 weeks, followed by valsartan 320 mg for 16 weeks. The valsartan dose was then tapered off to 80 mg for one week. Patients took valsartan film coated tablets orally once a day (od) in the morning.

After a second 2-week washout period, patients were treated with atenolol plus HCTZ for 20 weeks. Patients received atenolol 100 mg for 20 weeks. Patients took atenolol tablets orally once a day (od) in the morning. Patients received HCTZ 12.5 mg for 4 weeks starting at the beginning of the 5th week and then received 25 mg for 12 weeks. Patients took HCTZ tablets orally once a day (od) in the morning.

 Drug: Atenolol
100 mg tablets orally once a day (od) in the morning.
Drug: Hydrochlorothiazide (HCTZ))
12.5 or 25 mg tablets orally once a day (od) in the morning.
Drug: Valsartan
80 mg, 160 mg, or 320 mg tablets orally once a day in the morning
Experimental: Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan

After a 2-week washout period, patients were treated with atenolol plus HCTZ for 20 weeks followed by one week in which atenolol was tapered off and HCTZ was discontinued. Patients received atenolol 100 mg for 20 weeks. Patients took atenolol tablets orally once a day (od) in the morning. Patients received HCTZ 12.5 mg for 4 weeks starting at the beginning of the 5th week and then received 25 mg for 12 weeks. Patients took HCTZ tablets orally once a day (od) in the morning.

After a second 2-week washout period, patients were treated with valsartan for 20 weeks. Patients received valsartan 160 mg for 4 weeks, followed by valsartan 320 mg for 16 weeks. Patients took valsartan film coated tablets orally once a day (od) in the morning.

 Drug: Atenolol
100 mg tablets orally once a day (od) in the morning.
Drug: Hydrochlorothiazide (HCTZ))
12.5 or 25 mg tablets orally once a day (od) in the morning.
Drug: Valsartan
80 mg, 160 mg, or 320 mg tablets orally once a day in the morning

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00396656

Locations
Germany
Investigative Centers, Germany
Switzerland
Novartis Pharma Ag
Basel, Switzerland
Sponsors and Collaborators
Novartis
Investigators
Principal Investigator: Novartis Pharma Ag Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Anna Mitchell, MD, University Hospital Essen, Essen, Germany et al.
ClinicalTrials.gov Identifier: NCT00396656     History of Changes
Other Study ID Numbers: CVAH631BDE06
Study First Received: November 6, 2006
Results First Received: January 7, 2011
Last Updated: May 5, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
hypertension
valsartan
atenolol
hydrochlorothiazide
 microcirculation
arterial compliance
pulse wave analysis

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Atenolol
Valsartan
Hydrochlorothiazide
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
 Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on February 09, 2012



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