Hypertension
Conditions
Keywords
Hypertension, Left Ventricular Mass
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.
Interventions
DRUGNebivolol
Nebivolol 2.5 mg once daily
DRUGMetoprolol succinate
Metoprolol succinate 50 mg once daily
Sponsors
Forest Laboratories
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inappropriate Left Ventricular Mass (LVM) | 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%. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily.
Nebivolol: Nebivolol 2.5 mg once daily | 1 |
| Metoprolol Succinate Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily.
Metoprolol succinate: Metoprolol succinate 50 mg once daily | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Nebivolol | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 1 participants | 1 participants |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 1 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Change in Inappropriate Left Ventricular Mass (LVM)
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%.
Time frame: baseline, 6 months
Population: Data were not collected for the single participant, so no analysis was performed.