Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

This study has been terminated.
(Difficulty in identifying subjects satisfying the inclusion criteria.)
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Marek Belohlavek, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01605370
First received: May 22, 2012
Last updated: May 8, 2014
Last verified: May 2014

May 22, 2012
May 8, 2014
June 2012
March 2013   (final data collection date for primary outcome measure)
Change in Inappropriate Left Ventricular Mass (LVM) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
LVM will be measured by echocardiography exam. LVM is inappropriate when observed LVM (oLVM) exceeds predicted LVM (pLVM) by more than 28%, that is, 100×(oLVM/pLVM) >128%.
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].
Complete list of historical versions of study NCT01605370 on ClinicalTrials.gov Archive Site
Not Provided
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.
Not Provided
Not Provided
 
Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?
Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Hypertension
  • Drug: Nebivolol
    Nebivolol 2.5 mg once daily
    Other Name: Bystolic
  • Drug: Metoprolol succinate
    Metoprolol succinate 50 mg once daily
    Other Name: Toprol XL
  • Experimental: Nebivolol
    Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily.
    Intervention: Drug: Nebivolol
  • Metoprolol succinate
    Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily.
    Intervention: Drug: Metoprolol succinate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
March 2013
March 2013   (final data collection date for primary outcome measure)

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 the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines (JNC-7).

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.
Both
30 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01605370
11-007035
No
Marek Belohlavek, Mayo Clinic
Mayo Clinic
Forest Laboratories
Principal Investigator: Marek Belohlavek, MD, PhD Mayo Clinic
Mayo Clinic
May 2014

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