HypertensionPhase 2EVIDENCENCT01522950
A Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function
A Phase 2 study testing Nebivolol and atenolol in people with Hypertension, run by University of Minnesota at 1 site in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled study comparing the efficacy of nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular disease risk in subjects with early vascular disease. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Nebivolol and atenolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Oct 2016
- Phase
- Phase 2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- borderline blood pressure (120-145/80-90 mm Hg);
- borderline or abnormal small artery elasticity (C2) as measured by pulse contour analysis;
- treatment-naive for all blood pressure medications including diuretics for at least 30 days prior to baseline visit;
- able to walk on a treadmill for 3 minutes;
- female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device during and for 1 month after the last dose of study drug;
- voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Who cannot join
- history of intolerance to beta-blockers or clear contraindications to their use; current pharmaceutical treatment of blood pressure;
- known history of cardiovascular disease (myocardial infarction, coronary artery bypass graft, unstable angina, uncontrolled arrhythmias, stroke, etc.);
- known history of diabetes; known history of hepatic, renal or gastrointestinal disorder;
- known history of any illness that may cause additional risk (as determined by study investigator);
- pregnant or lactating women [when used during pregnancy, beta-blockers may cause fetal harm];
- participation in a concomitant clinical trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: A Double-blind, Placebo-controlled, Randomized Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function and Cardiovascular Risk in Patients With Early Vascular Disease
This is a randomized, double-blind, placebo-controlled study comparing the efficacy of nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular disease risk in subjects with early vascular disease. Approximately 75 subjects with borderline/elevated blood pressures and impaired endothelial function, as measured by arterial elasticity scores, will be recruited and assigned to treatment groups using a block randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo, and then followed for 9 months.
Read the detailed description
The Rasmussen Disease Score (RDS) test panel is the chosen methodology for this study. The 10 parameters of the RDS were selected because of their ability to quantify early structural and functional abnormalities in the vasculature and left ventricle which appear long before cardiovascular disease is present.
The RDS tests include: large and small artery elasticity (measured by pulse contour analysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and microalbuminuria. Quantitative results from these tests are converted into categorical classifications based on values stratified by age and gender when appropriate. The categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2 points. Point values from all parameters are summed to create the RDS, with values ranging from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced disease. Previous research has shown that the RDS is a powerful predictor of future cardiovascular events.
The small artery elasticity (C2) parameter is of particular interest as it is responsive to changes in NO levels and is an effective and reliable predictor of future hypertension and other cardiovascular events. Changes in C2 will serve as the primary outcome of this study. Similar studies using anti-hypertensive or lipid-lowering interventions have found significant improvements in C2 values.
Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index of endothelial function, although this method appears to be less sensitive to functional changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow comparison with previous studies and take advantage of a large sample size to further examine the relative sensitivity of each method for reliably measuring endothelial dysfunction.
The duration of intervention for this study is 9 months which is the minimum time to adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a critical component of a comprehensive assessment of cardiovascular health and have improved within this temporal window as a result of anti-hypertensive intervention.
- Conditions
- Hypertension
- Being tested
- Nebivolol, atenolol, placebo
- Keywords
- hypertension, prevention, endothelial function
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
5 mg daily or 10 mg daily
atenololDrug
25 mg daily or 50 mg daily
placeboDrug
one tablet daily
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol | Active comparator | 5 mg, continue for 1 month; dose titration to 10 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur. Receives: Drug: Nebivolol |
| Atenolol | Active comparator | 25 mg, continue for 1 month; dose titration to 50 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur. Receives: Drug: atenolol |
| Placebo | Placebo comparator | Continue for 1 month; dose titration to "high dose" placebo, continue for 8 months. Dose may be returned to initiation levels if side effects occur. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Small Artery Elasticity
Change in small artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation.
Measured: baseline, 9 months
Secondary outcomes (3)
Change in Large Artery Elasticity
Change in large artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation.
Measured: baseline, 9 months
Change in Systolic Blood Pressure
Change in systolic blood pressure as measured by sphygmomanometer from baseline to 9 months after intervention initiation.
Measured: baseline, 9 months
Change in Diastolic Blood Pressure
Change in diastolic blood pressure as measured by sphygmomanometer from baseline to 9 months after intervention initiation.
Measured: baseline, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startMay 2010
- Primary completionOct 2016
- Study completionOct 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Jay N Cohn, MD, Principal investigator, University of Minnesota Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522950
- Sponsor's protocol ID
- CV-2014-20226
- Acronym
- EVIDENCE
- Status last verified
- Jul 2020
- First submitted
- 17 Jan 2012
- Last updated
- 17 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Duprez DA, Florea N, Duval S, Koukol C, Cohn JN. Effect of nebivolol or atenolol vs. placebo on cardiovascular health in subjects with borderline blood pressure: the EVIDENCE study. J Hum Hypertens. 2017 Dec;32(1):20-25. doi: 10.1038/s41371-017-0019-9. Epub 2017 Nov 28.
PubMed 29184167
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Placebo-controlled, Randomized Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function and Cardiovascular Risk in Patients With Early Vascular Disease
- ClinicalTrials.gov ID
- NCT01522950
- Acronym / sponsor ID
- EVIDENCE / CV-2014-20226
- Conditions
- Hypertension
- Keywords
- hypertension, prevention, endothelial function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- May 2010
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 21 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, placebo-controlled study comparing the efficacy of nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular disease risk in subjects with early vascular disease. Approximately 75 subjects with borderline/elevated blood pressures and impaired endothelial function, as measured by arterial elasticity scores, will be recruited and assigned to treatment groups using a block randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo, and then followed for 9 months.
Detailed description
The Rasmussen Disease Score (RDS) test panel is the chosen methodology for this study. The 10 parameters of the RDS were selected because of their ability to quantify early structural and functional abnormalities in the vasculature and left ventricle which appear long before cardiovascular disease is present.
The RDS tests include: large and small artery elasticity (measured by pulse contour analysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and microalbuminuria. Quantitative results from these tests are converted into categorical classifications based on values stratified by age and gender when appropriate. The categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2 points. Point values from all parameters are summed to create the RDS, with values ranging from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced disease. Previous research has shown that the RDS is a powerful predictor of future cardiovascular events.
The small artery elasticity (C2) parameter is of particular interest as it is responsive to changes in NO levels and is an effective and reliable predictor of future hypertension and other cardiovascular events. Changes in C2 will serve as the primary outcome of this study. Similar studies using anti-hypertensive or lipid-lowering interventions have found significant improvements in C2 values.
Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index of endothelial function, although this method appears to be less sensitive to functional changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow comparison with previous studies and take advantage of a large sample size to further examine the relative sensitivity of each method for reliably measuring endothelial dysfunction.
The duration of intervention for this study is 9 months which is the minimum time to adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a critical component of a comprehensive assessment of cardiovascular health and have improved within this temporal window as a result of anti-hypertensive intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nebivolol | Active comparator | Drug: Nebivolol5 mg, continue for 1 month; dose titration to 10 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur. |
| Atenolol | Active comparator | Drug: atenolol25 mg, continue for 1 month; dose titration to 50 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur. |
| Placebo | Placebo comparator | Drug: placeboContinue for 1 month; dose titration to "high dose" placebo, continue for 8 months. Dose may be returned to initiation levels if side effects occur. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- borderline blood pressure (120-145/80-90 mm Hg);
- borderline or abnormal small artery elasticity (C2) as measured by pulse contour analysis;
- treatment-naive for all blood pressure medications including diuretics for at least 30 days prior to baseline visit;
- able to walk on a treadmill for 3 minutes;
- female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device during and for 1 month after the last dose of study drug;
Key exclusion criteria (6 listed)
- history of intolerance to beta-blockers or clear contraindications to their use; current pharmaceutical treatment of blood pressure;
- known history of cardiovascular disease (myocardial infarction, coronary artery bypass graft, unstable angina, uncontrolled arrhythmias, stroke, etc.);
- known history of diabetes; known history of hepatic, renal or gastrointestinal disorder;
- known history of any illness that may cause additional risk (as determined by study investigator);
- pregnant or lactating women [when used during pregnancy, beta-blockers may cause fetal harm];
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 |
|---|---|---|
| Nebivolol5 mg daily or 10 mg daily | Drug | Nebivolol |
| atenolol25 mg daily or 50 mg daily | Drug | Atenolol |
| placeboone tablet daily | Drug | Placebo |
Primary outcome
Change in Small Artery Elasticity
Time frame: baseline, 9 months
Change in small artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation.
3 secondary outcomes
Change in Large Artery Elasticity
Time frame: baseline, 9 months
Change in Systolic Blood Pressure
Time frame: baseline, 9 months
Change in Diastolic Blood Pressure
Time frame: baseline, 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29184167Duprez DA, Florea N, Duval S, Koukol C, Cohn JN. Effect of nebivolol or atenolol vs. placebo on cardiovascular health in subjects with borderline blood pressure: the EVIDENCE study. J Hum Hypertens. 2017 Dec;32(1):20-25. doi: 10.1038/s41371-017-0019-9. Epub 2017 Nov 28.
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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.
Jay N Cohn, MD principal investigator
University of Minnesota Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nebivolol and atenolol in people with Hypertension, run by University of Minnesota at 1 site in United States.
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 6 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 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Jan 2020). 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?
Change in Small Artery Elasticity (time frame: baseline, 9 months). 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 NCT01522950, which also lists 1 linked publication.
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 17 Jul 2020.