Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

This study has been terminated.
(Despite extended efforts, unexpected difficulties prevented identifying proper candidates for the study.)
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Marek Belohlavek, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01605370
First received: May 22, 2012
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to evaluate if a drug called nebivolol can reverse inappropriate left ventricular mass (LVM) when compared to the standard of care drug metoprolol.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Inappropriate LVM [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Presence of inappropriate LVM (if a previously clinically indicated echocardiography exam or other imaging method providing patient's LVM is available): LVM is inappropriate when observed LVM (oLVM) exceeds predicted LVM (pLVM) by more than 28%, that is, 100×(oLVM/pLVM) >128% [1].


Secondary Outcome Measures:
  • Echo measures of LV function [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    we will test whether ad-vanced echo measures of LV function are altered in the patients with LVM, and whether their values significantly change after treatment with nebivolol or metoprolol.


Enrollment: 1
Study Start Date: June 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nebivolol Drug: Nebivolol
Nebivolol 2.5 mg once daily
Other Name: Bystolic
Metoprolol succinate
Comparator from the same drug class, but without known vasodilating effects
Drug: Metoprolol succinate
Metoprolol succinate 50 mg once daily
Other Name: Toprol XL

Detailed Description:

In response to chronic pressure overload by arterial hypertension, the cardiac left ventricle undergoes hypertrophy, that is, increases its wall thickness and, therefore, its mass, to sustain the elevated workload. Such anatomical remodeling can be considered adaptive or appropriate. However, in a considerable number of patients with arterial hypertension, the increase in the left ventricular mass is excessive and, thus, inappropriate.

Ventricular mass is inappropriate when its amount surpasses the physical need of the ventricle to sustain the elevated workload. Therefore, ventricular mass can be inappropriate even in patients without arterial hypertension or without hypertrophy identified by echocardiography (echo). We can mathematically predict an appropriate amount of mass and observe the actual mass in individual patients based on ventricular workload and wall thickness, respectively, noninvasively evaluated by echo. By comparing the observed ventricular mass to the predicted one, we determine whether its amount is inappropriate. It follows that by therapeutically normalizing blood pressure in hypertension and thus eliminating the elevated workload, then any ventricular hypertrophy represents an inappropriate mass.

Inappropriate ventricular mass is proven to have a detrimental effect on long-term cardiovascular event-free survival, and ventricular hypertrophy is increasingly recognized as a potent risk factor of cardiovascular morbidity and mortality, and all-cause mortality. Ventricular performance is altered in hypertension with inappropriate mass, but this alteration can be subtle enough to escape detection using current echocardiography measures. Hence, patients with hypertension, who have inappropriate left ventricular mass, need to be specifically identified by analysis of the predicted and observed ventricular mass, and the therapeutic goal must include management of elevated blood pressure as well as reversal of the excessive ventricular mass.

In this double-blind prospective study, patients with hypertension and inappropriate ventricular mass will be randomized to therapy with nebivolol or metoprolol to find out whether nebivolol could reverse inappropriate left ventricular mass, thus providing a benefit beyond what is achieved by mere blood pressure reduction alone. If confirmed, this will represent a significant ancillary ability of nebivolol and be a key step towards therapy of inappropriate ventricular mass, which is a so far unmanaged cardiovascular risk and a poor event-free prognostic factor.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

All candidates must have previously untreated hypertension. The candidates will be picked from patients with stage-1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg) and those with stage-2 hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥100), based on JNC-7 guidelines.

Inclusion Criteria:

  • Presence of inappropriate LVM.
  • Presence of phenotype of inappropriate LVM.

Exclusion Criteria:

The criteria will assure that only patients with hypertension are enrolled, that is, excluded will be subjects with systolic BP < 140 or diastolic BP < 90 (ie, prehypertension or normal BP), but without complications or any indication (or suspicion) of end-organ damage based on a physical exam, clinical history, or laboratory tests.

Specific exclusion criteria are:

  • Reactive airways disease including asthma.
  • Diabetes mellitus or hypoglycemia; thyrotoxicosis.
  • LV dysfunction (ejection fraction < 50%) or heart failure.
  • Present or previously documented coronary heart disease or angina.
  • Acute myocardial infarction, or history of myocardial infarction.
  • Severe bradycardia, heart block greater than first degree or sick sinus syndrome (unless a permanent pacemaker is in place).
  • Hepatic insufficiency or history of cirrhosis.
  • Chronic renal failure or renovascular dysfunction.
  • Cerebrovascular dysfunction.
  • Peripheral vascular disease.
  • Pregnant or nursing women; women of childbearing age will be required to take a pregnancy test at the time of enrollment and use an acceptable method of birth control.
  • Poor echo image quality.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01605370

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Forest Laboratories
Investigators
Principal Investigator: Marek Belohlavek, MD, PhD Mayo Clinic
  More Information

No publications provided

Responsible Party: Marek Belohlavek, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01605370     History of Changes
Other Study ID Numbers: 11-007035
Study First Received: May 22, 2012
Last Updated: March 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Hypertension, Left Ventricular Mass

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Metoprolol
Nebivolol
Metoprolol succinate
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 beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on April 23, 2014