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

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”

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.

Intervention(s) in this Clinical Trial

• 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

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• 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.

Primary 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)
    Safety Issue?: No

Secondary 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• Mean Post-treatment Microcirculation at NaCl Injected Sites
  • Time Frame: At end of each treatment period (Week 21 and Week 43)
    Safety Issue?: No
• Arterial Pressure Waveform Augmentation Index at the End of Treatment
  • Time Frame: At end of each treatment period (Week 21 and Week 43)
    Safety Issue?: No
• Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment
  • Time Frame: At end of each treatment period (Week 21 and Week 43)
    Safety Issue?: No

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Novartis Pharma Ag Principal Investigator Novartis Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00396656

Study ID Number: CVAH631BDE06

ClinicalTrials.gov Identifier: NCT00396656

Health Authority: Germany: Federal Institute for Drugs and Medical Devices