HypertensionPhase 4NCT00999102
Nebivolol Versus Metoprolol: Comparative Effects on Fatigue and Quality of Life
A Phase 4 study testing Metoprolol and Nebivolol in people with Hypertension, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Beta-blockers are prescribed to millions of people for treatment of hypertension. Fatigue is a recognized and common side effect of beta-blockers that can have significant effects on quality of life. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Metoprolol and Nebivolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Jan 2011
- Phase
- Phase 4
- 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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals who are taking, or are about to begin taking, a beta-blocker, and who have the approved indication of hypertension
Who cannot join
- Orthopedic ailments that would interfere with performance of treadmill testing
- Stroke or heart attack within the previous 1 year
- Symptomatic coronary disease within the past year (angina, shortness of breath)
- Clinically significant pulmonary disease (e.g. emphysema or asthma).
- Poorly controlled hypertension (blood pressure above 160 systolic or 100 diastolic)
- Patients with contra-indications to taking a beta-blocker (asthma or bradyarrhythmia)
- History of tachyarrhythmia (abnormal rapid heart rate)
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life
Beta-blockers are prescribed to millions of people for treatment of hypertension. Fatigue is a recognized and common side effect of beta-blockers that can have significant effects on quality of life. Worse, many people taking a beta-blocker for years are not even aware of the reduction of energy with which they are living.
A new vasodilating beta-blocker, nebivolol, which is approved by the FDA for treatment of hypertension, appears to be far less associated with fatigue than are most currently available beta-blockers. The purpose of this study is to compare nebivolol with the current best-selling beta-blocker, metoprolol, and determine whether there is a significant difference in side effects including fatigue, reduced exertion tolerance, and reduced quality of life.
In this study, 30 subjects will take each of the 2 study drugs for 8 weeks, consisting of 4 weeks at a lower dose, and 4 weeks at a higher dose. All dosages are FDA-approved for treatment of hypertension. Subjects and investigators will not know which drug is being administered until completion of the study. Subjects will undergo a treadmill stress test and will complete fatigue and quality of life questionnaires after each 4 weeks of treatment. An echocardiogram and non-invasive measurement of aortic blood pressure will be performed after 8 weeks on each drug. Also, blood will be drawn and stored for possible measurement of drug levels, after 4 and 8 weeks on each drug. Results on each drug will then be compared. If nebivolol is found to cause significantly less fatigue, it would be of substantial importance to the many millions of people who are on life-long beta-blocker therapy, and are living with reduced energy.
Read the detailed description
- Hypothesis: the beta-blocker nebivolol is associated with less fatigue than metoprolol, the most widely-prescribed beta-blocker
- Methods: a double-blinded crossover trial comparing nebivolol with metoprolol. Experimental procedures: Subjects will undergo electrocardiogram and routine blood testing, unless such tests have been performed within 6 months and are available for review. Subjects entered into the study will receive each of the two study drugs for 8 weeks. Metoprolol succinate will be given at a dose of 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks. For nebivolol, dosage will be 5 mg daily for 4 weeks and 10mg daily for 4 weeks. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in period.
At the end of each 4-week treatment period on each drug, subjects will undergo a treadmill stress test (using the standard Cornell protocol), complete Quality of Life and fatigue questionnaires, and have blood drawn and frozen for later analysis for drug levels.
At the end of 8 weeks of treatment on each drug, subjects will undergo echocardiography and applanation tonometry (non-invasive measurement of aortic blood pressure) to assess heart function.
At the end of the study, the blinded subjects will be asked which of the two study drugs they preferred, and the extent to which their energy differed between the two drugs.
-Rationale: Millions of hypertensive patients are on life-long beta-blocker therapy. In many, it reduces cardiac output and increases peripheral resistance to blood flow (1). It is well-established that beta-blockers cause fatigue in many patients and reduce exertion tolerance. Every physician knows this, and tacitly accepts that many patients are living with this unwelcome side effect.
A new beta-blocker, nebivolol, has the standard beta-blocking effects, but also produces blood vessel relaxation (vasodilation), probably through increased secretion of the vasodilator nitric oxide. Studies indicate that nebivolol, unlike most beta-blockers, does not cause constriction of peripheral blood vessels, and is associated with improved heart function (2). Studies suggest that it is also less likely to cause fatigue (3).
Personal experience is consistent with this, as I have observed marked improvement in energy in patients in whom I have prescribed nebivolol in place of a different beta-blocker. The possibility of placebo effect of course cannot be excluded. Nevertheless, the known hemodynamic differences between nebivolol and other beta-blockers, and the positive clinical experience, warrant formal study to determine whether nebivolol is kinder than other beta-blockers in terms of the important side effect of fatigue.
- Conditions
- Hypertension
- Being tested
- Metoprolol, Nebivolol
- Keywords
- hypertension, beta blockers, Metoprolol, blood pressure, high, antihypertensive agents, vascular resistance, adrenergic beta-receptor blockaders, beta-Adrenergic blockers, beta-Adrenergic Blocking Agents, beta-Adrenergic Receptor Blockaders, beta-Blockers, Adrenergic, Bystolic, Nebivolol, Nebivololum, Nebivololum [Latin], R65,824, Beloc- Zok, H 93/26 succinate, Metoprolol succinate, Seloken ZOC
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetoprololDrug
Also called Lopressor, Toprol-XL
Metoprolol 50 mg, Metoprolol 100 mg,
NebivololDrug
Also called Bystolic
Nebivolol 5 mg, Nebivolol 10 mg.
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol, followed by Metoprolol | Experimental | Participants first received Nebivolol at a dose of 5 mg daily for 4 weeks, followed by 10 mg daily for another 4 weeks (i.e., weeks 1-8 in total). The participants then received Metoprolol at a dose of 50 mg daily for 4 weeks, followed by 100 mg daily for another 4 weeks (i.e., weeks 9-16 in total). Receives: Drug: Metoprolol; Drug: Nebivolol |
| Metoprolol, followed by Nebivolol | Experimental | Participants first received Metoprolol at a dose of 50 mg daily for 4 weeks, followed by 100 mg daily for another 4 weeks (i.e., weeks 1-8 in total). The participants then received Nebivolol at a dose of 5 mg daily for 4 weeks, followed by 10 mg daily for another 4 weeks (i.e., weeks 9-16 in total) Receives: Drug: Metoprolol; Drug: Nebivolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.
A 16 item scale that measures 4 dimensions of fatigue: severity, distress, timing, and degree of interference in activities of daily living.
Range: 1 (no fatigue) to 50 (extreme fatigue).
Measured: After 4 weeks of treatment on each drug/dose combination
Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.
Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination (in minutes). The Treadmill Test was Performed at the 4-week Visit of Each Drug/Dose Combination.
Measured: After 4 weeks of treatment on each drug/dose combination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2011
- Study completionJan 2011
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.
- More trials run by Weill Medical College of Cornell UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Samuel J Mann, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00999102
- Sponsor's protocol ID
- 0901010162
- Status last verified
- Oct 2018
- First submitted
- 20 Oct 2009
- Last updated
- 19 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life
- ClinicalTrials.gov ID
- NCT00999102
- Acronym / sponsor ID
- 0901010162
- Conditions
- Hypertension
- Keywords
- hypertension, beta blockers, Metoprolol, blood pressure, high, antihypertensive agents, vascular resistance, adrenergic beta-receptor blockaders, beta-Adrenergic blockers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Oct 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 21 Oct 2009 (estimated)
- Results
- Posted 19 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Beta-blockers are prescribed to millions of people for treatment of hypertension. Fatigue is a recognized and common side effect of beta-blockers that can have significant effects on quality of life. Worse, many people taking a beta-blocker for years are not even aware of the reduction of energy with which they are living.
A new vasodilating beta-blocker, nebivolol, which is approved by the FDA for treatment of hypertension, appears to be far less associated with fatigue than are most currently available beta-blockers. The purpose of this study is to compare nebivolol with the current best-selling beta-blocker, metoprolol, and determine whether there is a significant difference in side effects including fatigue, reduced exertion tolerance, and reduced quality of life.
In this study, 30 subjects will take each of the 2 study drugs for 8 weeks, consisting of 4 weeks at a lower dose, and 4 weeks at a higher dose. All dosages are FDA-approved for treatment of hypertension. Subjects and investigators will not know which drug is being administered until completion of the study. Subjects will undergo a treadmill stress test and will complete fatigue and quality of life questionnaires after each 4 weeks of treatment. An echocardiogram and non-invasive measurement of aortic blood pressure will be performed after 8 weeks on each drug. Also, blood will be drawn and stored for possible measurement of drug levels, after 4 and 8 weeks on each drug. Results on each drug will then be compared. If nebivolol is found to cause significantly less fatigue, it would be of substantial importance to the many millions of people who are on life-long beta-blocker therapy, and are living with reduced energy.
Detailed description
- Hypothesis: the beta-blocker nebivolol is associated with less fatigue than metoprolol, the most widely-prescribed beta-blocker
- Methods: a double-blinded crossover trial comparing nebivolol with metoprolol. Experimental procedures: Subjects will undergo electrocardiogram and routine blood testing, unless such tests have been performed within 6 months and are available for review. Subjects entered into the study will receive each of the two study drugs for 8 weeks. Metoprolol succinate will be given at a dose of 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks. For nebivolol, dosage will be 5 mg daily for 4 weeks and 10mg daily for 4 weeks. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in period.
At the end of each 4-week treatment period on each drug, subjects will undergo a treadmill stress test (using the standard Cornell protocol), complete Quality of Life and fatigue questionnaires, and have blood drawn and frozen for later analysis for drug levels.
At the end of 8 weeks of treatment on each drug, subjects will undergo echocardiography and applanation tonometry (non-invasive measurement of aortic blood pressure) to assess heart function.
At the end of the study, the blinded subjects will be asked which of the two study drugs they preferred, and the extent to which their energy differed between the two drugs.
-Rationale: Millions of hypertensive patients are on life-long beta-blocker therapy. In many, it reduces cardiac output and increases peripheral resistance to blood flow (1). It is well-established that beta-blockers cause fatigue in many patients and reduce exertion tolerance. Every physician knows this, and tacitly accepts that many patients are living with this unwelcome side effect.
A new beta-blocker, nebivolol, has the standard beta-blocking effects, but also produces blood vessel relaxation (vasodilation), probably through increased secretion of the vasodilator nitric oxide. Studies indicate that nebivolol, unlike most beta-blockers, does not cause constriction of peripheral blood vessels, and is associated with improved heart function (2). Studies suggest that it is also less likely to cause fatigue (3).
Personal experience is consistent with this, as I have observed marked improvement in energy in patients in whom I have prescribed nebivolol in place of a different beta-blocker. The possibility of placebo effect of course cannot be excluded. Nevertheless, the known hemodynamic differences between nebivolol and other beta-blockers, and the positive clinical experience, warrant formal study to determine whether nebivolol is kinder than other beta-blockers in terms of the important side effect of fatigue.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nebivolol, followed by Metoprolol | Experimental | Drug: Metoprolol, Drug: NebivololParticipants first received Nebivolol at a dose of 5 mg daily for 4 weeks, followed by 10 mg daily for another 4 weeks (i.e., weeks 1-8 in total). The participants then received Metoprolol at a dose of 50 mg daily for 4 weeks, followed by 100 mg daily for another 4 weeks (i.e., weeks 9-16 in total). |
| Metoprolol, followed by Nebivolol | Experimental | Drug: Metoprolol, Drug: NebivololParticipants first received Metoprolol at a dose of 50 mg daily for 4 weeks, followed by 100 mg daily for another 4 weeks (i.e., weeks 1-8 in total). The participants then received Nebivolol at a dose of 5 mg daily for 4 weeks, followed by 10 mg daily for another 4 weeks (i.e., weeks 9-16 in total) |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Individuals who are taking, or are about to begin taking, a beta-blocker, and who have the approved indication of hypertension
Key exclusion criteria (7 listed)
- Orthopedic ailments that would interfere with performance of treadmill testing
- Stroke or heart attack within the previous 1 year
- Symptomatic coronary disease within the past year (angina, shortness of breath)
- Clinically significant pulmonary disease (e.g. emphysema or asthma).
- Poorly controlled hypertension (blood pressure above 160 systolic or 100 diastolic)
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 |
|---|---|---|
| MetoprololAlso: Lopressor, Toprol-XLMetoprolol 50 mg, Metoprolol 100 mg, | Drug | Metoprolol, followed by Nebivolol, Nebivolol, followed by Metoprolol |
| NebivololAlso: BystolicNebivolol 5 mg, Nebivolol 10 mg. | Drug | Metoprolol, followed by Nebivolol, Nebivolol, followed by Metoprolol |
Primary outcome
Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.
Time frame: After 4 weeks of treatment on each drug/dose combination
A 16 item scale that measures 4 dimensions of fatigue: severity, distress, timing, and degree of interference in activities of daily living. Range: 1 (no fatigue) to 50 (extreme fatigue).
Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.
Time frame: After 4 weeks of treatment on each drug/dose combination
Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination (in minutes). The Treadmill Test was Performed at the 4-week Visit of Each Drug/Dose Combination.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hypertension
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
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.
Samuel J Mann, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metoprolol and Nebivolol in people with Hypertension, run by Weill Medical College of Cornell University 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 1 inclusion and 7 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 19 Oct 2018. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 19 Oct 2018). 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?
Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination. (time frame: After 4 weeks of treatment on each drug/dose combination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2018.