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Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients? (Inapprop)

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ClinicalTrials.gov Identifier: NCT01605370
Recruitment Status : Terminated (Difficulty in identifying subjects satisfying the inclusion criteria.)
First Posted : May 24, 2012
Results First Posted : May 7, 2014
Last Update Posted : May 19, 2014
Forest Laboratories
Information provided by (Responsible Party):
Marek Belohlavek, Mayo Clinic

Brief Summary:
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 or disease Intervention/treatment Phase
Hypertension Drug: Nebivolol Drug: Metoprolol succinate Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?
Study Start Date : June 2012
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Arm Intervention/treatment
Experimental: Nebivolol
Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily.
Drug: Nebivolol
Nebivolol 2.5 mg once daily
Other Name: Bystolic

Metoprolol succinate
Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily.
Drug: Metoprolol succinate
Metoprolol succinate 50 mg once daily
Other Name: Toprol XL

Primary Outcome Measures :
  1. Change in Inappropriate Left Ventricular Mass (LVM) [ Time Frame: baseline, 6 months ]
    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%.

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01605370

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United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Forest Laboratories
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Principal Investigator: Marek Belohlavek, MD, PhD Mayo Clinic
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Responsible Party: Marek Belohlavek, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01605370    
Other Study ID Numbers: 11-007035
First Posted: May 24, 2012    Key Record Dates
Results First Posted: May 7, 2014
Last Update Posted: May 19, 2014
Last Verified: May 2014
Keywords provided by Marek Belohlavek, Mayo Clinic:
Hypertension, Left Ventricular Mass
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Anti-Arrhythmia Agents
Antihypertensive Agents
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
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists