Hypertension
Conditions
Brief summary
Hypertension, or high blood pressure, is a common disease that affects many Americans, and can lead to devastating consequences such as heart attack, stroke, and death if not treated. Nebivolol is a medication that has been recently approved by the FDA for the treatment of hypertension. Nebivolol has an unusual profile compared to other medications, in that its effects may be related to release of a substance called nitric oxide. Nitric oxide is released from the cells lining the blood vessels, and nebivolol may stimulate these cells to release more nitric oxide. Our study will investigate whether treatment with nebivolol, as compared to another medication called metoprolol, in hypertensive subjects will be more effective in protecting blood vessels against the harmful effects of high blood pressure. The mechanisms we will investigate include oxidative stress markers and circulating levels of endothelial progenitor cells.
Interventions
DRUGNebivolol
Nebivolol 5 mg PO qday for 2 weeks, titrated up to Nebivolol 10 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Nebivolol 20 mg PO qday if BP is \>125/80 for the remaining 8 weeks
DRUGMetoprolol succinate
Metoprolol 50 mg PO qday for 2 weeks, titrated up to Metoprolol 100 mg PO qday if BP is \>125/80 for the 2 more weeks, and then titrated up to Metoprolol 200 mg PO qday if BP is \>125/80 for the remaining 8 weeks
Sponsors
Forest Laboratories
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males or post-menopausal females aged 21-80 years. 2. Hypertensive patients (BP \>135/85) will be eligible to participate. 3. Patients on current anti-hypertensive therapy that does not include beta blockade should have BP \>135/85. 4. Patients on anti-hypertensive therapy including beta blockade will have their beta blockers discontinued gradually over 2 weeks before enrolment. 5. Concomitant therapy: Patients will be allowed to be on comcomitant therapy with aspirin, statins, thiazide diuretics, calcium antagonists (for treatment of hypertension), clonidine, vasodilators, or angiotensin antagonists. Patients will be on stable medical therapy for at least 2 months before recruitment. Patients with previous treatment with beta adrenergic blockers (metoprolol, propranolol, atenolol, and labetalol) will also be eligible to participate, but will be randomized to the study beta blocker.
Exclusion criteria
1. Age \< 21 or \>80 years 2. Initiation or change in dose of statin or anti-hypertensive therapy within 2 months before the study 3. Premenopausal females with potential for pregnancy 4. Acute infection in previous 2 weeks 5. History of substance abuse 6. Current neoplasm 7. Chronic renal failure \[creatinine \> 2.5 mg/dL\] or liver failure (Liver enzymes \>2X normal) 8. Acute coronary syndrome, Class IV heart failure, CVA, coronary intervention within 2 months 9. Known aortic stenosis, hypertrophic cardiomyopathy. 10. Inability to give informed consent 11. Inability to return to Emory for follow-up testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulse Wave Velocity (Measure of Arterial Stiffness) | Baseline | The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). |
Countries
United States
Participant flow
Recruitment details
Patients recruited from clinic sites at Emory University Hospital and by advertisements between December 2009 through April 2012.
Pre-assignment details
There were 96 subjects enrolled. 58 of the subjects were withdrawn prior to group assignment. 39 subjects did not meet eligibility criteria and 19 subjects withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol/ Metoprolol Subjects were randomized to nebivolol for 3 months. They crossed over to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80. | 16 |
| Metoprolol/Nebivolol Subjects were randomized to metoprolol succinate for 3 months. They crossed over to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80. | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 (3 Months) | Adverse Event | 0 | 2 |
| Treatment Period 2 (3 Months) | Lost to Follow-up | 3 | 3 |
Baseline characteristics
| Characteristic | Nebivolol/ Metoprolol | Metoprolol/Nebivolol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 12 Participants | 28 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 2 / 19 |
Outcome results
Primary
Pulse Wave Velocity (Measure of Arterial Stiffness)
The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol/ Metoprolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 9.4 meters per second (m/s) | Standard Deviation 2.6 |
| Metoprolol/Nebivolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 8.9 meters per second (m/s) | Standard Deviation 1.5 |
Primary
Pulse Wave Velocity (Measure of Arterial Stiffness)
The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol/ Metoprolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 8.4 meters per second (m/s) | Standard Deviation 2.4 |
| Metoprolol/Nebivolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 10.1 meters per second (m/s) | Standard Deviation 1.4 |
Primary
Pulse Wave Velocity (Measure of Arterial Stiffness)
The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol/ Metoprolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 9.1 meters per second (m/s) | Standard Deviation 2.2 |
| Metoprolol/Nebivolol | Pulse Wave Velocity (Measure of Arterial Stiffness) | 9.8 meters per second (m/s) | Standard Deviation 1.6 |