Trial Outcomes & Findings for Safety and Efficacy of Valsartan vs Atenolol and Hydrochlorothiazide Combination on Blood Flow in Hypertensive Patients (NCT NCT00396656)
NCT ID: NCT00396656
Last Updated: 2011-06-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
30 participants
Primary outcome timeframe
At end of each treatment period (Week 21 and Week 43)
Results posted on
2011-06-06
Participant Flow
Participant milestones
| Measure |
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.
|
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
|
|---|---|---|
|
First Treatment Period
STARTED
|
15
|
15
|
|
First Treatment Period
COMPLETED
|
15
|
13
|
|
First Treatment Period
NOT COMPLETED
|
0
|
2
|
|
Second Treatment Period
STARTED
|
15
|
13
|
|
Second Treatment Period
COMPLETED
|
15
|
12
|
|
Second Treatment Period
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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
|
|---|---|---|
|
First Treatment Period
Withdrawal by Subject
|
0
|
2
|
|
Second Treatment Period
Adverse Event
|
0
|
1
|
Baseline Characteristics
Safety and Efficacy of Valsartan vs Atenolol and Hydrochlorothiazide Combination on Blood Flow in Hypertensive Patients
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=30 Participants
Includes patients that received valsartan followed by atenolol + hydrochlorothiazide and patients that received atenolol + hydrochlorothiazide followed by valsartan.
|
|---|---|
|
Age Continuous
|
52.3 years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Injected Sites Compared to NaCl Injected Sites
|
61.21 Perfusion units
Standard Deviation 38.11
|
61.04 Perfusion units
Standard Deviation 49.16
|
SECONDARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Difference in Mean Post-treatment Microcirculation at Acetylcholine (ACH) Plus L-NMMA Injected Sites Compared to NaCl Injected Sites
|
-9.11 Perfusion units
Standard Deviation 22.19
|
-5.60 Perfusion units
Standard Deviation 40.47
|
SECONDARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Difference in Mean Post-treatment Microcirculation at a Sodium Nitroprusside Injected Site Compared to NaCl Injected Sites
|
120.65 Perfusion units
Standard Deviation 74.52
|
128.14 Perfusion units
Standard Deviation 63.79
|
SECONDARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Mean Post-treatment Microcirculation at NaCl Injected Sites
|
44.78 Perfusion units
Standard Deviation 47.53
|
50.96 Perfusion units
Standard Deviation 67.88
|
SECONDARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Arterial Pressure Waveform Augmentation Index at the End of Treatment
|
139.05 Ratio
Standard Deviation 20.64
|
144.51 Ratio
Standard Deviation 21.97
|
SECONDARY outcome
Timeframe: At end of each treatment period (Week 21 and Week 43)Population: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.
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.
Outcome measures
| Measure |
Valsartan
n=27 Participants
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.
|
Atenolol + Hydrochlorothiazide
n=27 Participants
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.
|
|---|---|---|
|
Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment
|
8.07 Meters per second
Standard Deviation 1.28
|
7.60 Meters per second
Standard Deviation 1.18
|
Adverse Events
Valsartan
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Atenolol + Hydrochlorothiazide
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Valsartan
n=28 participants at risk
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.
|
Atenolol + Hydrochlorothiazide
n=30 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Diverticulitis
|
0.00%
0/28
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.
|
3.3%
1/30
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.
|
Other adverse events
| Measure |
Valsartan
n=28 participants at risk
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.
|
Atenolol + Hydrochlorothiazide
n=30 participants at risk
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.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
10.7%
3/28
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.
|
6.7%
2/30
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
1/28
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.
|
6.7%
2/30
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.
|
|
General disorders
Chest pain
|
0.00%
0/28
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.
|
6.7%
2/30
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.
|
|
Infections and infestations
Bronchitis
|
7.1%
2/28
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.
|
3.3%
1/30
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.
|
|
Infections and infestations
Cystitis
|
7.1%
2/28
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.
|
3.3%
1/30
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.
|
|
Infections and infestations
Otitis externa
|
0.00%
0/28
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.
|
6.7%
2/30
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.
|
|
Infections and infestations
Sinusitis
|
7.1%
2/28
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.
|
3.3%
1/30
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.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
2/28
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.
|
3.3%
1/30
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.6%
1/28
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.
|
6.7%
2/30
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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.1%
2/28
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.
|
0.00%
0/30
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.6%
1/28
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.
|
6.7%
2/30
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.
|
|
Nervous system disorders
Headache
|
10.7%
3/28
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.
|
20.0%
6/30
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.
|
|
Vascular disorders
Hypotension
|
7.1%
2/28
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.
|
0.00%
0/30
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.
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862 778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER