A Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function (EVIDENCE)
This is a randomized, double-blind, placebo-controlled study comparing the efficacy of nebivolol and atenolol at improving small artery elasticity and reducing cardiovacular disease risk in subjects with early vascular disease. Approximately 75 subjects with borderline/elevated blood pressures and impaired endothelial function, as measured by arterial elasticity scores, will be recruited and assigned to treatment groups using a block randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo, and then followed for 9 months.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-blind, Placebo-controlled, Randomized Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function and Cardiovascular Risk in Patients With Early Vascular Disease|
- Comparing effects of nebivolol against atenolol and placebo on endothelial function [ Time Frame: 9 months ] [ Designated as safety issue: No ]Change in small artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation.
- Evaluate effects of nebivolol as compared to atenolol and placebo [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Change in RDS from 0 to 3 and 9 months. Each test is scored 0/normal, 1/borderline, and 2/abnormal. The ten CV tests provide total score 0 to 20.
Change in each of the CDS components as measured from baseline to 3 and 9 months.
Change in risk factors and biomarkers.
Difference in endothelial function quantification and sensitivity of pulse contour analysis and flow-mediated dilation.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Nebivolol
5 mg, continue for 1 month; dose titration to 10 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur.
5 mg daily or 10 mg daily
Active Comparator: Atenolol
25 mg, continue for 1 month; dose titration to 50 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur.
25 mg daily or 50 mg daily
Placebo Comparator: Placebo
Continue for 1 month; dose titration to "high dose" placebo, continue for 8 months. Dose may be returned to initiation levels if side effects occur.
one tablet daily
The Rasmussen Disease Score (RDS) test panel is the chosen methodology for this study. The 10 parameters of the RDS were selected because of their ability to quantify early structural and functional abnormalities in the vasculature and left ventricle which appear long before cardiovascular disease is present.
The RDS tests include: large and small artery elasticity (measured by pulse contour anlysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and microalbuminuria. Quantitative results from these tests are converted into categorical classifications based on values stratified by age and gender when appropriate. The categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2 points. Point values from all parameters are summed to create the RDS, with values ranging from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced disease. Previous research has shown that the RDS is a powerful predictor of future cardiovascular events.
The small artery elasticity (C2) parameter is of particular interest as it is responsive to changes in NO levels and is an effective and reliable predictor of future hypertension and other cardiovascular events. Changes in C2 will serve as the primary outcome of this study. Similar studies using anti-hypertensive or lipid-lowerng interventions have found significant improvements in C2 values.
Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index of endothelial function, although this method appears to be less sensitive to functional changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow comparison with previous studies and take advantage of a large sample size to further examine the relative sensitivity of each method for reliably measuring endothelial dysfunction.
The duration of intervention for this study is 9 months which is the minimum time to adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a critical component of a comprehensive assessment of cardiovascular health and have improved within this temporal window as a result of anti-hypertensive intervention.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01522950
|Contact: Jay N Cohn, MDfirstname.lastname@example.org|
|United States, Minnesota|
|University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Catherine Kraft Koukol 612-626-2807 email@example.com|