Clinical trial NCT00999102: Nebivolol Versus Metoprolol: Comparative Effects on Fatigue and Quality of Life
Official title: Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
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
Selozok
Spesicor Dos
Toprol XL
Toprol-XL
UNII-TH25PD4CCB
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2009-10-21
Enrollment: 37
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* Individuals who are taking, or are about to begin taking, a beta-blocker, and who have the approved indication of hypertension

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.
timeFrame: After 4 weeks of treatment on each drug/dose combination
measure: Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.
timeFrame: After 4 weeks of treatment on each drug/dose combination
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Samuel J Mann, MD
role: PRINCIPAL_INVESTIGATOR
References: