HypertensionPhase 3NCT00396656

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

A Phase 3 study testing Atenolol, Hydrochlorothiazide (HCTZ)) and Valsartan in people with Hypertension, run by Novartis at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 40 to 65 years
Conditions the study is for: Hypertension
What is being tested?: Atenolol, Hydrochlorothiazide (HCTZ)) and Valsartan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 2 sitesin 2 countries
Study dates: Dec 2005to Dec 2007
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Germany1 site

Study site
Investigative Centers

Other trials in Germany

Switzerland1 site

Novartis Pharma Ag
Basel

Other trials in Switzerland

About this study

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.

Conditions: Hypertension
Being tested: Atenolol, Hydrochlorothiazide (HCTZ)), Valsartan
Keywords: hypertension, valsartan, atenolol, hydrochlorothiazide, microcirculation, arterial compliance, pulse wave analysis
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT00396656
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Atenolol; Drug: Hydrochlorothiazide (HCTZ)); Drug: Valsartan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
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.
Measured: 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
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.
Measured: At end of each treatment period (Week 21 and Week 43)
Mean Post-treatment Microcirculation at NaCl Injected Sites
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.
Measured: At end of each treatment period (Week 21 and Week 43)
Arterial Pressure Waveform Augmentation Index at the End of Treatment
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.
Measured: At end of each treatment period (Week 21 and Week 43)
Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment
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.
Measured: At end of each treatment period (Week 21 and Week 43)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2005Dec 2007

First posted7 Nov 2006 (estimated)
Study startDec 2005
Primary completionDec 2007
Study completionDec 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00396656
Sponsor's protocol ID: CVAH631BDE06
Status last verified: May 2011
First submitted: 6 Nov 2006
Last updated: 6 Jun 2011
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00396656
Acronym / sponsor ID: CVAH631BDE06
Conditions: Hypertension
Keywords: hypertension, valsartan, atenolol, hydrochlorothiazide, microcirculation, arterial compliance, pulse wave analysis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Study start: Dec 2005
Primary completion: Dec 2007 (actual)
Study completion: Dec 2007 (actual)
First posted: 7 Nov 2006 (estimated)
Results: Posted 6 Jun 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)	Experimental	Drug: Atenolol, Drug: Hydrochlorothiazide (HCTZ)), Drug: ValsartanAfter 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	Experimental	Drug: Atenolol, Drug: Hydrochlorothiazide (HCTZ)), Drug: ValsartanAfter 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.

Who may qualify

Ages: 40 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Atenolol100 mg tablets orally once a day (od) in the morning.	Drug	Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan, Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)
Hydrochlorothiazide (HCTZ))12.5 or 25 mg tablets orally once a day (od) in the morning.	Drug	Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan, Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)
Valsartan80 mg, 160 mg, or 320 mg tablets orally once a day in the morning	Drug	Atenolol + hydrochlorothiazide (HCTZ) followed by valsartan, Valsartan followed by atenolol + hydrochlorothiazide (HCTZ)

Primary outcome

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)
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.

5 secondary outcomes

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)
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)
Mean Post-treatment Microcirculation at NaCl Injected Sites
Time frame: At end of each treatment period (Week 21 and Week 43)
Arterial Pressure Waveform Augmentation Index at the End of Treatment
Time frame: At end of each treatment period (Week 21 and Week 43)
Arterial Pressure Waveform Pulse Wave Velocity at the End of Treatment
Time frame: At end of each treatment period (Week 21 and Week 43)

Results and safety

Results posted to the registry on 6 Jun 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Valsartan Followed by Atenolol + Hydrochlorothiazide (HCTZ)	15	15
Atenolol + Hydrochlorothiazide (HCTZ) Followed by Valsartan	15	13

Primary outcome: 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). Mean (Standard Deviation). Unit: Perfusion units

Measure	Valsartan n = 27	Atenolol + Hydrochlorothiazide n = 27
Value	61.21 (38.11)	61.04 (49.16)

Population analysed: Intent-to-treat (ITT) population: All randomized patients with at least one valid post-baseline primary efficacy measurement in both treatment periods.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Valsartan	0 of 28 (0%)	16 of 28 (57.1%)	Not reported
Atenolol + Hydrochlorothiazide	1 of 30 (3.3%)	12 of 30 (40%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharma Ag principal investigator

Novartis Pharmaceuticals

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atenolol, Hydrochlorothiazide (HCTZ)) and Valsartan in people with Hypertension, run by Novartis at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00396656.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2011.