Nebivolol Versus Metoprolol: Comparative Effects on Fatigue and Quality of Life

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00999102
First received: October 20, 2009
Last updated: March 16, 2012
Last verified: March 2012

October 20, 2009
March 16, 2012
October 2009
January 2011   (final data collection date for primary outcome measure)
  • To determine whether fatigue scores differ during treatment with nebivolol versus metoprolol succinate [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ] [ Designated as safety issue: No ]
  • To determine whether treadmill exercise time differs during treatment with nebivolol versus metoprolol succinate [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00999102 on ClinicalTrials.gov Archive Site
Not Provided
To determine whether there are differences between the two drugs as far as the following parameters: resting and exercise heart rate, resting and exercise blood pressure, left ventricular systolic function, wall stress, calculated aortic pressure [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks, 16 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Nebivolol Versus Metoprolol: Comparative Effects on Fatigue and Quality of Life
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 ata 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.

  • 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 2 study drug 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 and 10mg daily. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in.

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 2 study drugs they prefer, and the extent to which their energy differed between the 2 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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Hypertension
  • Drug: Metoprolol
    Comparison of Metoprolol and Nebivolol. 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 and 10mg daily. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in.
    Other Names:
    • Lopressor
    • Toprol-XL
  • Drug: Nebivolol
    Comparison of Metoprolol and Nebivolol. 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 and 10mg daily. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in.
    Other Name: Bystolic
  • Active Comparator: Nebivolol then Metoprolol

    Nebivolol will be given at a dose of 5 mg and 10mg daily. After 8 weeks, participants will then be given metoprolol succinate will be given at a dose of 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks.Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in. 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.

    Interventions:
    • Drug: Metoprolol
    • Drug: Nebivolol
  • Active Comparator: Metoprolol then Nebivolol

    Metoprolol succinate will be given at a dose of 50 mg daily for 4 weeks, then 100 mg daily for 4 weeks. After 8 weeks, the participants will take nebivolol, dosage will be 5 mg and 10mg daily. Identical-appearing pills will be given, and the drugs will be given in randomized order without a placebo run-in. 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.

    Interventions:
    • Drug: Metoprolol
    • Drug: Nebivolol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
37
January 2011
January 2011   (final data collection date for primary outcome measure)

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)
Both
21 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00999102
0901010162
No
Samuel Mann, MD, Weill Cornell Medical College
Weill Medical College of Cornell University
Forest Laboratories
Principal Investigator: Samuel J Mann, MD Weill Medical College of Cornell University
Weill Medical College of Cornell University
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP