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Trial record 27 of 116 for:    Atenolol

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

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ClinicalTrials.gov Identifier: NCT00396656
Recruitment Status : Completed
First Posted : November 7, 2006
Results First Posted : June 6, 2011
Last Update Posted : June 6, 2011
Sponsor:
Information provided by:
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypertension
Interventions Drug: Atenolol
Drug: Hydrochlorothiazide (HCTZ))
Drug: Valsartan
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Valsartan Followed by Atenolol + Hydrochlorothiazide (HCTZ) Atenolol + Hydrochlorothiazide (HCTZ) Followed by Valsartan
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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.

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

Period Title: First Treatment Period
Started 15 15
Completed 15 13
Not Completed 0 2
Reason Not Completed
Withdrawal by Subject             0             2
Period Title: Second Treatment Period
Started 15 13
Completed 15 12
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Arm/Group Title Entire Study Population
Hide Arm/Group Description Includes patients that received valsartan followed by atenolol + hydrochlorothiazide and patients that received atenolol + hydrochlorothiazide followed by valsartan.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
52.3  (7.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
11
  36.7%
Male
19
  63.3%
1.Primary Outcome
Title Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Injected Sites Compared to NaCl Injected Sites
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Perfusion units
61.21  (38.11) 61.04  (49.16)
2.Secondary Outcome
Title Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Plus L-NMMA Injected Sites Compared to NaCl Injected Sites
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Perfusion units
-9.11  (22.19) -5.60  (40.47)
3.Secondary Outcome
Title Difference in Mean Post-treatment Microcirculation at a Sodium Nitroprusside Injected Site Compared to NaCl Injected Sites
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Perfusion units
120.65  (74.52) 128.14  (63.79)
4.Secondary Outcome
Title Mean Post-treatment Microcirculation at NaCl Injected Sites
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Perfusion units
44.78  (47.53) 50.96  (67.88)
5.Secondary Outcome
Title Arterial Pressure Waveform Augmentation Index at the End of Treatment
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Ratio
139.05  (20.64) 144.51  (21.97)
6.Secondary Outcome
Title Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment
Hide Description 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.
Time Frame At end of each treatment period (Week 21 and Week 43)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description:
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.
Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Meters per second
8.07  (1.28) 7.60  (1.18)
Time Frame [Not Specified]
Adverse Event Reporting Description Two patients in the treatment sequence atenolol + hydrochlorothiazide followed by valsartan did not receive treatment during the second treatment period and were excluded from the valsartan safety population analysis set.
 
Arm/Group Title Valsartan Atenolol + Hydrochlorothiazide
Hide Arm/Group Description 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. Patients received atenolol 100 mg for 19 weeks. In the last week of this intervention, the atenolol dose was reduced to 50 mg. Patients took atenolol tablets orally once a day (od) in the morning. Patients received hydrochlorothiazide 100 mg for 15 weeks starting at the beginning of the 5th week of this intervention. In the last week of this intervention, the hydrochlorothiazide dose was increased to 25 mg. Patients took hydrochlorothiazide tablets orally once a day (od) in the morning.
All-Cause Mortality
Valsartan Atenolol + Hydrochlorothiazide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Valsartan Atenolol + Hydrochlorothiazide
Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)   1/30 (3.33%) 
Infections and infestations     
Diverticulitis  1  0/28 (0.00%)  1/30 (3.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Valsartan Atenolol + Hydrochlorothiazide
Affected / at Risk (%) Affected / at Risk (%)
Total   16/28 (57.14%)   12/30 (40.00%) 
Ear and labyrinth disorders     
Vertigo  1  3/28 (10.71%)  2/30 (6.67%) 
Gastrointestinal disorders     
Diarrhoea  1  1/28 (3.57%)  2/30 (6.67%) 
General disorders     
Chest pain  1  0/28 (0.00%)  2/30 (6.67%) 
Infections and infestations     
Bronchitis  1  2/28 (7.14%)  1/30 (3.33%) 
Cystitis  1  2/28 (7.14%)  1/30 (3.33%) 
Otitis externa  1  0/28 (0.00%)  2/30 (6.67%) 
Sinusitis  1  2/28 (7.14%)  1/30 (3.33%) 
Upper respiratory tract infection  1  2/28 (7.14%)  1/30 (3.33%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/28 (3.57%)  2/30 (6.67%) 
Musculoskeletal pain  1  2/28 (7.14%)  0/30 (0.00%) 
Pain in extremity  1  1/28 (3.57%)  2/30 (6.67%) 
Nervous system disorders     
Headache  1  3/28 (10.71%)  6/30 (20.00%) 
Vascular disorders     
Hypotension  1  2/28 (7.14%)  0/30 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862 778-8300
Layout table for additonal information
Responsible Party: Anna Mitchell, MD, University Hospital Essen, Essen, Germany et al.
ClinicalTrials.gov Identifier: NCT00396656     History of Changes
Other Study ID Numbers: CVAH631BDE06
First Submitted: November 6, 2006
First Posted: November 7, 2006
Results First Submitted: January 7, 2011
Results First Posted: June 6, 2011
Last Update Posted: June 6, 2011