A Randomized Controlled Study to Assess the Effects of Bisoprolol and Atenolol on Resting Heart Rate and Sympathetic Nervous System's Activity in Subjects With Essential Hypertension

Study Overview
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Brief Summary
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This is a Phase 4, prospective, multi-centric and randomized controlled study to compare the effects of bisoprolol and atenolol on resting heart rate (RHR) and sympathetic nervous system's (SNS) activity in subjects with essential hypertension.

Official Title
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Effects of Bisoprolol and Atenolol on Resting Heart Rate and Sympathetic Nervous System's Activity in Patients With Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Bisoprolol
* Drug: Atenolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged between 25-65 years Subjects with essential hypertension (EH) Subjects with systolic blood pressure (SBP) 140-160 millimeter of mercury (mmHg) and diastolic blood pressure (DBP) 90-100 mmHg Subjects with normal sinus rhythm Subjects with resting heart rate (RHR) greater than 70 bpm Subjects who give written informed consent Exclusion Criteria: Subjects with atrial fibrillation (AF)/sick sinus syndrome (SSS)/atrioventricular block II-III Grade (AVB II-III) without pacemaker Subjects with bradyarrhythmia/hypotension Subjects with unstable angina pectoris (UAP)/acute myocardial infarction (AMI)/heart failure (HF) (New York Heart Association [NYHA] Class III - IV) Subjects with uncontrolled diabetes mellitus (DM) Subjects with bronchial asthma Subjects with gastro-intestinal ulcer or skin ulcer Subjects with liver dysfunction/renal impairment Subjects treated with calcium channel blockers (except amlodipine) or other beta-blockers. Subjects with glaucoma Subjects with known allergic/intolerance to beta-blocker Pregnant or lactating women Subjects who had participated in another clinical study within the last 3 months Subjects who have legal incapacity or limited legal capacity

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bisoprolol<br> | Drug: Bisoprolol<br>* Bisoprolol will be administered at a dose of 5 milligram (mg) once daily for 2 weeks. If heart rate is less than or equal to 65 beats per minute (bpm), then the initial dose will be administered for another 2 weeks. If the heart rate remains greater than 65 bpm, then the dose will be further increased to 7.5 mg once daily for 2 weeks. After 2 weeks, if the heart rate is less than or equal to 65 bpm, the increased dose will be administered for another 2 weeks. If the heart rate is still greater than 65 bpm, then the dose will be further increased to 10 mg once daily for 2 weeks. After 2 weeks, if the heart rate is less than or equal to 65 bpm, the increased dose will be administered for another 2 weeks.<br>* Other names: Concor®;|
| Active Comparator: Atenolol<br> | Drug: Atenolol<br>* Atenolol will be administered at a dose of 50 mg once daily for 2 weeks. If heart rate is less than or equal to 65 bpm, then the initial dose will be administered for another 2 weeks. If the heart rate remains greater than 65 bpm, then the dose will be further increased to 75 mg once daily for 2 weeks. After 2 weeks, if the heart rate is less than or equal to 65 bpm, the increased dose will be administered for another 2 weeks. If the heart rate still greater than 65 bpm, then the dose will be further increased to 100 mg once daily for 2 weeks. After 2 weeks, If the heart rate is less than or equal to 65 bpm, the increased dose will be administered for another 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal | Baroreflex sensitivity (BRS) is an important characteristic of baroreflex control and often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Heart rate goal was defined as attainment of heart rate less than or equal to 65 beats per minute (bpm). | Baseline and attainment of heart rate goal (Week 2 or Week 4 or Week 6) | 
| Change From Baseline in Baroreflex Sensitivity (BRS) at End of Follow-up | Baroreflex sensitivity (BRS) is an important characteristic of baroreflex control and often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. | Baseline and end of follow-up (Week 4 or Week 6 or Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Heart Rate Variability (HRV) for Low Frequency Power (LF) and for High Frequency Power (HF) at Attainment of Heart Rate Goal and End of Follow-up | Heart rate variability (HRV) is used to describe the variations of both instantaneous HR and resting rate (RR) intervals and was evaluated for low frequency power (LF) and for high frequency power (HF). Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. | Baseline, attainment of heart rate goal (Week 2 or Week 4 or Week 6) and end of follow-up (Week 4 or Week 6 or Week 8) | 
| Change From Baseline in Ratio of Heart Rate Variability (HRV) for Low Frequency Power (LF) to Heart Rate Variability Power (HRV) for High Frequency (HF) (LF/HF) at Attainment of Heart Rate Goal and End of Follow-up | Heart rate variability (HRV) is used to describe the variations of both instantaneous HR and resting rate (RR) intervals and was evaluated for low frequency power (LF) and for high frequency power (HF). Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. | Baseline, attainment of heart rate goal (Week 2 or Week 4 or Week 6) and end of follow-up (Week 4 or Week 6 or Week 8) | 
| Number of Participants Attaining Heart Rate Goal at Dosage 1, 2 and 3 of Study Treatment | Dosage 1, 2 and 3 for bisoprolol group was defined as 5 mg, 7.5 mg and 10 mg once daily and for atenolol group as 50 mg, 75 mg and 100 mg once daily, respectively. Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. | Baseline up to attainment of heart rate goal (Week 2 or Week 4 or Week 6) | 
| Percentage of Participants Attaining Heart Rate Goal at Week 2, 4 and 6 | Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. | Attainment of heart rate goal (Week 2 or Week 4 or Week 6) | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition | Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) | 
| Number of Participants Compliant With Study Treatment | Participants compliant with study treatment were the participants who have completed the study treatment regimen. | Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Bisoprolol, Atenolol