Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

NCT ID: NCT01605370

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-03-31

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.

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nebivolol

Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily.

Group Type: EXPERIMENTAL

Nebivolol

Intervention Type: DRUG

Nebivolol 2.5 mg once daily

Metoprolol succinate

Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily.

Group Type: OTHER

Metoprolol succinate

Intervention Type: DRUG

Metoprolol succinate 50 mg once daily

Interventions

Nebivolol

Nebivolol 2.5 mg once daily

Intervention Type: DRUG

Metoprolol succinate

Metoprolol succinate 50 mg once daily

Intervention Type: DRUG

Other Intervention Names

Bystolic; Toprol XL

Eligibility Criteria

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.

• 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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Marek Belohlavek

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marek Belohlavek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Countries

United States

Other Identifiers

11-007035

Identifier Type: -

Identifier Source: org_study_id