Clinical trial NCT01248338: Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function
Official title: Comparison the Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function and Large Artery Stiffness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: Berlin-Chemie AG Menarini Group
Sponsor class: INDUSTRY
First posted: 2010-11-25
Enrollment: 80
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effects of nebivolol and metoprolol on endothelial function
timeFrame: 12 months
Secondary outcomes:
measure: Change in carotid artery intima-media thickness
timeFrame: 12 months
measure: Change in left ventricular mass index, systolic and diastolic function
timeFrame: 12 months
measure: Arterial Compliance
timeFrame: 12 months
Other outcomes:
Locations:
city: Tartu
country: Estonia
facility: Cardiology Clinic of Tartu University Clinics
Study officials:
affiliation: Cardiology Clinic of Tartu University Clinics
name: Jaan Eha, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.