Nebivolol Versus Metoprolol: Sodium Sensitivity

NCT00992056 | Completed Phase 4 Results

• 1 other identifier: 20090654
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in 24-hour Mean Systolic Blood Pressure by ABPM From Day 5 of Low Sodium to Day 10 of High Sodium

  Day 5, Day 10

Study Arms (2)

Metoprolol/Nebivolol

EXPERIMENTAL

Metoprolol/Nebivolol: Metoprolol 50 mg titrated to 100 mg then nebivolol 5 mg titrated to 10 mg

Drug: nebivolol; Drug: Metoprolol

Nebivolol/Metoprolol

EXPERIMENTAL

Metoprolol 50 mg titrated to 100 mg then Nebivolol 5 mg titrated to 10 mg

Drug: nebivolol; Drug: Metoprolol

Interventions

nebivolol DRUG

5 mg titrated to 10 mg daily versus matching placebo

Also known as: Bystolic

Metoprolol/Nebivolol; Nebivolol/Metoprolol

Metoprolol DRUG

Metoprolol 50 mg titrated to 100 mg

Also known as: Toprol

Metoprolol/Nebivolol; Nebivolol/Metoprolol

Eligibility Criteria

• Age: 46 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women \> 45 years of age.
• Self-identified as Hispanic ethnicity.
• Have hypertension defined as:
• Systolic blood pressure 140-159 mm Hg off antihypertensive medications
• Diastolic 90-99 mm Hg off antihypertensive medications
• 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
• 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.
• No clinically significant or unstable coexisting medical condition in the estimation of the study PI
• No clinically significant abnormalities of physical exam or laboratory data in the estimation of the PI
• Concomitant medications will be evaluated on a case by case basis by the study PI
• Renal function as assessed by a Cockcroft-Gault estimated glomerular filtration rate (GFR) of \>70 ml/min
• Signed informed consent and the ability to understand the study and its procedures

You may not qualify if:

• Inability to understand the study or provide informed consent
• History of adverse effects or intolerance to nebivolol or beta-blockers
• Previous treatment with nebivolol within the preceding six months.
• Significant or unstable cardiovascular, pulmonary, renal, gastrointestinal, hepatic, endocrine, or central nervous system as determined by the principal investigator.
• Clinically significant abnormalities of physical examination or laboratory data as determined by the principal investigator.
• 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.
• 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.
• Grapefruit and Seville oranges are not allowed at any time during the study.
• Any disease or condition that, in the opinion of the investigator, could compromise the absorption, accumulation, metabolism, or excretion of the study medication.
• Current alcohol or drug abuse.
• Smoking of more than 10 cigarettes per day.

Sponsors & Collaborators

• University of Miami: lead
• Forest Laboratories: collaborator

Study Sites (1)

Division of Clinical Pharmacology Clinical Pharmacology Research Unit (CPRU) 1500 NW 12th Ave 15-West.

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Metoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenoxypropanolamines; Propanolamines; Propanols

Results Point of Contact

• Title: Richard A Preston MD MSPH MBA
• Organization: University of Miami

rpreston@med.miami.edu

305 243 5930

Study Officials

• Richard A Preston, MD MSPH MBA

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of Clinical Pharmacology

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 8, 2009
• Study Start: December 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: May 1, 2012
• Last Updated: June 8, 2017
• Results First Posted: June 23, 2014

Record last verified: 2017-05

Locations

US (1)