Echocardiographic Study of a Single Dose Bisoprolol Versus Nebivolol in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, crossover study in healthy adult subjects. Each subject will receive a single dose of bisoprolol 5 mg p.o. and nebivolol 5 mg p.o. with 1 week washout period. All subjects will undergo a physical examination, 12-lead electrocardiography and a comprehensive echocardiographic study before the administration of the study drug and 5 hours thereafter.

Official Title
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Echocardiographic Study of a Single Dose Bisoprolol Versus Nebivolol in Healthy Subjects: a Randomized, Double-blind, Cross-over Study

Conditions
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Bisoprolol Adverse Reaction, Nebivolol Adverse Reaction

Intervention / Treatment
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* Drug: Bisoprolol versus Nebivolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects (male and female) Age interval: 20-60 years old (inclusive) Exclusion Criteria: Any known absolute or relative contraindication to beta-blocker therapy Poor echogenicity A resting heart rate <60 bpm A resting blood pressure < 110/70 mmHg

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bisoprolol first, Nebivolol Second<br>In this arm, patient will first receive bisoprolol, and after 1 week washout period, nebivolol | Drug: Bisoprolol versus Nebivolol<br>* All subjects will receive both drugs, but at different time periods determined by randomization, with 1 week washout period<br>|
| Experimental: Nebivolol first, Bisoprolol second<br>In this arm, patient will first receive nebivolol, and after 1 week washout period, bisoprolol | Drug: Bisoprolol versus Nebivolol<br>* All subjects will receive both drugs, but at different time periods determined by randomization, with 1 week washout period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change (%) of cardiac output (CO) | CO (l/min), will be assessed by calculating stroke volume using pulsed-wave doppler (velocity time integral) | Pre- and 5 hours post study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute and relative changes of left ventricular ejection fraction (%) | Ejection fraction will be measured using modified Simpson rule | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of global longitudinal strain (%) | Global longitudinal strain will be assessed using speckle tracking echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of myocardial work (%) | Myocardial work will be assessed by using a dedicated commercially available software (GE, Norway) | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of atrial function (ml) | Atrial function will be assessed by measuring phasic volume changes during diastole | Pre- and 5 hours post study drug administration | 
| Absolute change of myocardial dispersion (ms) | Myocardial dispersion will be assessed by using speckle tracking echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of TAPSE (tricuspid annular plane systolic excursion, mm) | TAPSE will be assessed by M-mode echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of blood pressure (mmHg) | Brachial blood pressure will be measured by sphygmomanometer | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes in atrial strain (%) | Atrial strain will be assessed using speckle tracking echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of electrical dispersion (ms) | Electrical dispersion will be assessed by using 12-lead electrocardiogram | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of right ventricular fractional area change (%) | The parameter will be assessed by two-dimensional echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of heart rate (bpm) | Heart rate will be measured by 12-lead electrocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of left ventricular twist (%) | Twist will be assessed by speckle tracking echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of QTc interval (ms) | QTc interval will be measured by using 12-lead electrocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of mitral E/A ratio (%) | E/A ratio will be assessed by pulsed-wave Doppler | Pre- and 5 hours post study drug administration | 
| Absolute and relative change of mitral E/e prime ratio (%) | E/e prime ratio will be assessed by pulsed-wave and tissue Doppler echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative change of mitral E-wave deceleration time (ms) | E-wave deceleration time will be measured by pulsed-wave Doppler echocardiography | Pre- and 5 hours post study drug administration | 
| Absolute and relative changes of right ventricular global longitudinal strain (%) | Global strain will be assessed by using speckle tracking echocardiography | Pre- and 5 hours post study drug administration |