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
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Metoprolol
Drug: Nebivolol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • 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 ]

Enrollment: 37
Study Start Date: October 2009
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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: 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.

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

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 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.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999102

Locations
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
Sponsors and Collaborators
Weill Medical College of Cornell University
Forest Laboratories
Investigators
Principal Investigator: Samuel J Mann, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Samuel Mann, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT00999102     History of Changes
Other Study ID Numbers: 0901010162
Study First Received: October 20, 2009
Last Updated: March 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
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

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Metoprolol
Nebivolol
Metoprolol succinate
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on September 18, 2014