Effects of Nebivolol on Subclinical Left Ventricular dySfunction: A Comparative Study Against Metoprolol (ENESYS)
Primary Purpose
Primary Arterial Hypertension
Status
Completed
Phase
Phase 3
Locations
Romania
Study Type
Interventional
Intervention
Nebilet
Corvitol
Sponsored by
About this trial
This is an interventional treatment trial for Primary Arterial Hypertension focused on measuring arterial hypertension
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
Sites / Locations
- University and Emergency Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Nebivolol
Metoprolol
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Global systolic function (ejection fraction)
Radial myocardial velocities
Right ventricular function
Global diastolic function
Left ventricular mass index
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00942487
Brief Title
Effects of Nebivolol on Subclinical Left Ventricular dySfunction: A Comparative Study Against Metoprolol
Acronym
ENESYS
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
2. Study Status
Record Verification Date
July 2009
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Berlin-Chemie Menarini
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
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.
SECONDARY:
Global systolic function (ejection fraction)
Radial myocardial velocities
Right ventricular function
Global diastolic function
Left ventricular mass index
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Arterial Hypertension
Keywords
arterial hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nebivolol
Arm Type
Experimental
Arm Title
Metoprolol
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Nebilet
Intervention Description
Trade-mark: Nebilet® (Berlin-Chemie Menarini) INN: nebivolol Dosage and route of administration: 5 mg tablets, o.d. for oral administration
Intervention Type
Drug
Intervention Name(s)
Corvitol
Intervention Description
Trade-mark: Corvitol (Berlin-Chemie Menarini) INN: metoprolol Dosage and route of administration: 50 mg tablets, b.d. (100 mg/day) for oral administration
Primary Outcome Measure Information:
Title
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Global systolic function (ejection fraction)
Time Frame
6 months
Title
Radial myocardial velocities
Time Frame
6 months
Title
Right ventricular function
Time Frame
6 months
Title
Global diastolic function
Time Frame
6 months
Title
Left ventricular mass index
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dragos VINEREANU, MD
Organizational Affiliation
University and Emergency Hospital Bucharest, Romania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University and Emergency Hospital
City
Bucharest
ZIP/Postal Code
050098
Country
Romania
12. IPD Sharing Statement
Citations:
PubMed Identifier
21827541
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.
Results Reference
derived
PubMed Identifier
21297499
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.
Results Reference
derived
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Effects of Nebivolol on Subclinical Left Ventricular dySfunction: A Comparative Study Against Metoprolol
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