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

NCT00396656 | Completed Phase 3 Results

• 1 other identifier: CVAH631BDE06
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hypertension

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  At end of each treatment period (Week 21 and Week 43)

Secondary Outcomes (5)

• 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)

• 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)

• Mean Post-treatment Microcirculation at NaCl Injected Sites

  At end of each treatment period (Week 21 and Week 43)

• Arterial Pressure Waveform Augmentation Index at the End of Treatment

  At end of each treatment period (Week 21 and Week 43)

• Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment

  At end of each treatment period (Week 21 and Week 43)

Study Arms (2)

Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

EXPERIMENTAL

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; Drug: Hydrochlorothiazide (HCTZ)); Drug: Valsartan

Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan

EXPERIMENTAL

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; Drug: Hydrochlorothiazide (HCTZ)); Drug: Valsartan

Interventions

Atenolol DRUG

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

Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan; Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

Hydrochlorothiazide (HCTZ)) DRUG

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

Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan; Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

Valsartan DRUG

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

Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan; Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis: lead

Study Sites (2)

Unknown Facility

Investigative Centers, Germany

Location

Novartis Pharma Ag

Basel, Switzerland

Location

MeSH Terms

Conditions

Hypertension

Interventions

Atenolol; Hydrochlorothiazide; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharma Ag

  Novartis Pharmaceuticals

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 6, 2006
• First Posted: November 7, 2006
• Study Start: December 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: June 6, 2011
• Results First Posted: June 6, 2011

Record last verified: 2011-05

Locations

DE (1); CH (1)