Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function (NEMENDAS)

Comparison the Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function and Large Artery Stiffness

An impairment of endothelial function plays the central role in the pathogenesis of cardiovascular diseases and their complications. Most of cardiovascular risk factors are known to impair endothelial function and the established disease further aggravates endothelial dysfunction.

The aim of the present study is to investigate the effects of nebivolol or metoprolol succinate on endothelial function and large artery stiffness.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: metoprolol succinate; Drug: Nebivolol

Detailed Description

The aim of this study was to compare the effects between the vasodilating β-blocker nebivolol and the cardioselective β-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study in 80 hypertensive patients. Patients received either nebivolol 5 mg or metoprolol succinate 50-100 mg daily for one year. Their heart rate, central and brachial blood pressure, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity and left ventricular wall thickness were measured at baseline and at the end of the study.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Estonia
  • Tartu, Estonia, 51014
    • Cardiology Clinic of Tartu University Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with mild to moderate essential hypertension (systolic BP 140-179 mmHg and/or diastolic BP 90-109 mmHg)*
• Male and female patients aged 30-65 years Newly diagnosed untreated patients or previously diagnosed patients who were without treatment at least two weeks prior to screening* If patient has been taken previously antihypertensive medication the BP values are originated after untreated two weeks before randomization

Exclusion Criteria:

• Concomitant medication: Cyclic antidepressants, MAO inhibitors, corticosteroids
• Diabetes I or II type (fasting venous plasma glucose > 6.4 mmol/l)
• Bronchial asthma and chronic obstructive airway disease
• Body mass index > 30 kg/m2
• Ischaemic heart disease (III, IV stage, Canadian Cardiovascular Society)
• Clinically relevant heart failure (NYHA class II - IV)
• Clinically relevant valve disease (physical examination)
• Arrhythmias and conduction disturbances, requiring therapy, sinus bradycardia at rest < 50 b/min, sick sinus syndrome, AV - block stage II - III
• Secondary hypertension (urea >8.3 mmol/l, creatinine >120μmol/l (males), >103 μmol/l (females), TSH > 4.0mIU/l, free T4 > 27 pmol/l)
• Clinically relevant atherosclerotic disease of lower extremities
• Acute inflammation (according to CRP > 10mg/l)
• Hypercholesterolemia (> 6,5 mmol/l)
• Allergic reaction to beta-blockers
• Pregnant or breast-feeding women
• History of hepatic, renal, metabolic or endocrine diseases
• Smoking > 10 cigarettes per day
• Alcohol consumption > 7 drinks per week (drink = 0,33 l beer, 120 ml wine or 30 ml strong alcoholic drink)
• The patient has had surgery or disease of the gastrointestinal tract which, in the opinion of the investigator, may influence the absorption or elimination of the study drug.
• The patient has a severe organic disorder that may interfere with the absorption, pharmacokinetics, or elimination of the study medication.
• The patient has a comorbid condition that would be expected to result in death during the trial period (e.g., terminal cancer, AIDS).
• The patient has chronic psychoses or behavioural conditions that would limit the ability of the patient to comply with the requirements of this study.
• The patient has known hypersensitivity to Nebivolol, Metoprolol or hydrochlorothiazide related compounds.
• Patient is enrolled in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: metoprolol, tablets; metoprolol succinate 50-100 mg orally daily for one year	Drug: metoprolol succinate; once daily 50 or 100 mg for one year; Other Names: Corvitol
Experimental: nebivolol; nebivolol 5 mg capsule once daily for one year	Drug: Nebivolol; once daily 5 mg capsule for one year; Other Names: Nebilet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of nebivolol and metoprolol on endothelial function	High-fidelity micromanometer (applanation tonometry) from both wrists and PWA, which is to be performed of the systolic portion (SphygmoCor Px, version 7.0) of the pulse curve.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in carotid artery intima-media thickness	Ultrasound scanner,with an 12 MHz transducer. Longitudinal images from 3 projections (anterolateral, lateral, and posterolateral) are measured for the common carotid artery, carotid bulb, and internal carotid artery	12 months
Change in left ventricular mass index, systolic and diastolic function	2-dimensional echocardiography using the standard apical 4-chamber view	12 months
Arterial Compliance	Peripheral blood pressure and arterial waveform to be measured in the dominant arm by a Cardiovascular Profiling Instrument	12 months

Collaborators and Investigators

• Sponsor: Berlin-Chemie AG Menarini Group
• Investigators: Principal Investigator: Jaan Eha, Professor, Cardiology Clinic of Tartu University Clinics

Publications and helpful links

General Publications

• Serg M, Kampus P, Kals J, Zagura M, Zilmer M, Zilmer K, Kullisaar T, Eha J. Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension. Scand J Clin Lab Invest. 2012 Sep;72(5):427-32. doi: 10.3109/00365513.2012.691991. Epub 2012 Jun 18.
• Kampus P, Serg M, Kals J, Zagura M, Muda P, Karu K, Zilmer M, Eha J. Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness. Hypertension. 2011 Jun;57(6):1122-8. doi: 10.1161/HYPERTENSIONAHA.110.155507. Epub 2011 May 2.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 19, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimate): November 25, 2010

Study Record Updates

• Last Update Posted (Estimate): November 25, 2010
• Last Update Submitted That Met QC Criteria: November 24, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Metoprolol
• Other Study ID Numbers: MeES/05/Neb-EnD/001