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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Bisoprolol Adverse Reaction; Nebivolol Adverse Reaction
• Intervention / Treatment: Drug: Bisoprolol versus Nebivolol

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Serbia
  • Belgrade, Serbia, 11080
    • Clinical Hospital Centre Zemun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects (male and female)
2. Age interval: 20-60 years old (inclusive)

Exclusion Criteria:

1. Any known absolute or relative contraindication to beta-blocker therapy
2. Poor echogenicity
3. A resting heart rate <60 bpm
4. A resting blood pressure < 110/70 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Clinical Hospital Center Zemun

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2030
• Primary Completion (Anticipated): December 1, 2030
• Study Completion (Anticipated): December 1, 2030

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Estimate): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; 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; Bisoprolol; Nebivolol
• Other Study ID Numbers: 01-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No