Clinical trial NCT00942487: Effects of Nebivolol on Subclinical Left Ventricular dySfunction: A Comparative Study Against Metoprolol
Official title: Effects of NEbivolol on Subclinical Left Ventricular dYSfunction. A Comparative Study Against Metoprolol. The ENESYS Study. A Phase 3, Randomised, Parallel, Active-controlled, Open Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Arterial Hypertension
Keywords: arterial hypertension
Lead sponsor: Berlin-Chemie Menarini
Sponsor class: INDUSTRY
First posted: 2009-07-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Summary:

* Study title: Effects of Nebivolol on subclinical left ventricular dysfunction. A comparative study against Metoprolol. (ENESYS study)
* Study phase: 3
* Study design (parallel, cross-over, etc.), randomisation and blinding procedures, type of control (placebo or active): randomised, parallel, active-controlled, open label
* Study treatment(s)/drug(s): Nebivolol versus Metoprolol
* Patients:

  * characteristics: patients with hypertension and left ventricular hypertrophy
  * planned total number: 50
* Study duration:

  * total enrolment period (months): 18
  * treatment period (months): 6
  * follow up period (months): 6
* Total study duration (months): 24

  * Number of Centres: 1
  * Country(ies): Romania (RO)

Detailed description: STUDY OBJECTIVES

1. PRIMARY:

   * Longitudinal myocardial velocities at rest (assessed by tissue Doppler echocardiography)
   * Systolic functional reserve (calculated as the absolute and relative increase of the myocardial systolic velocities at peak stress from rest)
   * Brain natriuretic peptide (BNP, NT-pro BNP) after a 6-months period of treatment with nebivolol versus metoprolol. An improvement of more than 20% of the myocardial resting velocities of systolic functional reserve is considered to be clinically relevant. The working hypothesis is that the improvement of subclinical left ventricular dysfunction after 6 months of treatment is going to be greater in patients who receive nebivolol than in those who receive metoprolol.
2. SECONDARY:

   * Global systolic function (ejection fraction)
   * Radial myocardial velocities
   * Right ventricular function
   * Global diastolic function
   * Left ventricular mass index

Eligibility criteria: Inclusion Criteria:

* aged 18 years or older, men and women, hospitalized and outpatients
* with a history of primary arterial hypertension
* with a daytime ambulatory blood pressure \>140 and/or \>90 mm Hg
* with left ventricular hypertrophy: LVMI \> 125 g/m2 for men, and \> 110 g/m2 for women, by Devereux formula, as recommended by the ESH-ESC guidelines (14)
* in sinus rhythm
* consented, by signing the Informed Consent

Exclusion Criteria:

* Severe arterial hypertension (systolic blood pressure \> 180 mm Hg and/or diastolic blood pressure \> 110 mm Hg)
* Any history of coronary heart disease (stable angina, acute coronary syndromes, myocardial infarction)
* Any history of cerebrovascular disease
* Renal impairment (creatinine \> 1.5 mg% for men, \> 1.4 mg% for women)
* Left ventricular global systolic dysfunction (EF \< 45%)
* More than mild valvar (mitral or aortic) regurgitation
* Hypertrophic cardiomyopathy
* Pericarditis
* Cor pulmonale
* Pregnancy or lactating women
* Any significant co-morbidities
* Contraindication to beta-blocker therapy
* Concomitant treatment with other beta-blockers
* Participation to another investigational study in the last 3 months

Primary outcomes:
measure: Changes of: longitudinal myocardial velocities at rest (assessed by TDE), systolic functional reserve (calculated as the absolute and relative increase of the myocardial systolic velocities at peak stress from rest), NT-proBNP
timeFrame: 6 months
Secondary outcomes:
measure: Global systolic function (ejection fraction)
timeFrame: 6 months
measure: Radial myocardial velocities
timeFrame: 6 months
measure: Right ventricular function
timeFrame: 6 months
measure: Global diastolic function
timeFrame: 6 months
measure: Left ventricular mass index
timeFrame: 6 months
Other outcomes:
Locations:
city: Bucharest
country: Romania
facility: University and Emergency Hospital
Study officials:
affiliation: University and Emergency Hospital Bucharest, Romania
name: Dragos VINEREANU, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vinereanu D, Madler CF, Gherghinescu C, Ciobanu AO, Fraser AG. Cumulative impact of cardiovascular risk factors on regional left ventricular function and reserve: progressive long-axis dysfunction with compensatory radial changes. Echocardiography. 2011 Sep;28(8):813-20. doi: 10.1111/j.1540-8175.2011.01456.x. Epub 2011 Aug 9.
citation: Vinereanu D, Gherghinescu C, Ciobanu AO, Magda S, Niculescu N, Dulgheru R, Dragoi R, Lautaru A, Cinteza M, Fraser AG. Reversal of subclinical left ventricular dysfunction by antihypertensive treatment: a prospective trial of nebivolol against metoprolol. J Hypertens. 2011 Apr;29(4):809-17. doi: 10.1097/HJH.0b013e3283442f37.