Nebivolol Versus Metoprolol: Sodium Sensitivity

• Status: Completed
• Trial end date: 2012-05-01
• Target enrollment: 0
• Participant gender: Female

Summary

Research objectives

The objective of this randomized, placebo-controlled, 2 period crossover clinical trial is to determine the effects of nebivolol versus metoprolol on ambulatory blood pressure, the blood pressure response to dietary sodium loading, and renal handling of an acute sodium load in postmenopausal women with hypertension.

Hypothesis

Nebivolol will result in a blunted response of blood pressure to oral sodium administration and improved renal handling of an intravenous sodium load in comparison with metoprolol in hypertensive postmenopausal women.

Research plan

Study design

The study consisted of a randomized crossover trial of the effects on sodium sensitivity and renal sodium handling of nebivolol versus metoprolol. All study procedures were carried out under the direct supervision of the Principal Investigator in the outpatient and inpatient research unit of the University of Miami Division of Clinical Pharmacology.

Primary endpoint

Change in 24-hour mean systolic blood pressure determined by 24-hour ambulatory blood pressure monitor (ABPM) from the final day of low sodium to the final day of high sodium in nebivolol versus metoprolol

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Miami
• Collaborator: Forest Laboratories
• Treatments: Metoprolol; Nebivolol

Criteria

Inclusion Criteria:

1. Women > 45 years of age.

2. Self-identified as Hispanic ethnicity.

3. Have hypertension defined as:

• Systolic blood pressure 140-159 mm Hg off antihypertensive medications

• Diastolic 90-99 mm Hg off antihypertensive medications

4. Blood pressure will be calculated as the mean of 3 consecutive office cuff measurements at rest (sitting). In order to be eligible for treatment, subjects must meet the above definition of hypertension at screening visits off antihypertensive medications

5. Natural menopause at least 1 year (no menstruation for 1 year) prior to screening or had a bilateral oophorectomy at least 3 months prior to study participation.

6. No clinically significant or unstable coexisting medical condition in the estimation of the study PI

7. No clinically significant abnormalities of physical exam or laboratory data in the estimation of the PI

8. Concomitant medications will be evaluated on a case by case basis by the study PI

9. Renal function as assessed by a Cockcroft-Gault estimated glomerular filtration rate (GFR) of >70 ml/min

10. Signed informed consent and the ability to understand the study and its procedures

Exclusion Criteria:

1. Inability to understand the study or provide informed consent

2. History of adverse effects or intolerance to nebivolol or beta-blockers

3. Previous treatment with nebivolol within the preceding six months.

4. Significant or unstable cardiovascular, pulmonary, renal, gastrointestinal, hepatic, endocrine, or central nervous system as determined by the principal investigator.

5. Clinically significant abnormalities of physical examination or laboratory data as determined by the principal investigator.

6. The subject has donated or lost more than 450 mL of blood or has received transfusion of any blood or blood products within 30 days prior to screening.

7. Receiving treatment with diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, steroids, or other agents known to influence blood pressure, renal function, or sodium sensitivity. Any concomitant medications will be reviewed by the study PI on a case-by-case basis. In general, no concomitant medication is preferred. Any medication may be tapered/discontinued with consent of patient and at the discretion of the study PI.

8. Grapefruit and Seville oranges are not allowed at any time during the study.

9. Any disease or condition that, in the opinion of the investigator, could compromise the absorption, accumulation, metabolism, or excretion of the study medication.

10. Current alcohol or drug abuse.

11. Smoking of more than 10 cigarettes per day.