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

This study has been completed.
Sponsor:
Collaborator:
Merck Serono Co., Ltd., China
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01251146
First received: November 30, 2010
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Bisoprolol
Drug: Atenolol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Bisoprolol and Atenolol on Resting Heart Rate and Sympathetic Nervous System's Activity in Patients With Essential Hypertension

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal [ Time Frame: Baseline and attainment of heart rate goal (Week 2 or Week 4 or Week 6) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Baroreflex Sensitivity (BRS) at End of Follow-up [ Time Frame: Baseline and end of follow-up (Week 4 or Week 6 or Week 8) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Attaining Heart Rate Goal at Dosage 1, 2 and 3 of Study Treatment [ Time Frame: Baseline up to attainment of heart rate goal (Week 2 or Week 4 or Week 6) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Attaining Heart Rate Goal at Week 2, 4 and 6 [ Time Frame: Attainment of heart rate goal (Week 2 or Week 4 or Week 6) ] [ Designated as safety issue: No ]
    Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants Compliant With Study Treatment [ Time Frame: Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) ] [ Designated as safety issue: No ]
    Participants compliant with study treatment were the participants who have completed the study treatment regimen.


Enrollment: 177
Study Start Date: November 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bisoprolol Drug: Bisoprolol
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.
Other Name: Concor®
Active Comparator: Atenolol Drug: Atenolol
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.

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01251146

Locations
China
Beijing Shi Jingshan Hospital
Beijing, China
Shanghai Institute of Hypertension
Shanghai, China
Sponsors and Collaborators
Merck KGaA
Merck Serono Co., Ltd., China
Investigators
Principal Investigator: Gao Pingjin, Prof. Shanghai Institute of Hypertension
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01251146     History of Changes
Other Study ID Numbers: EMR200006-515
Study First Received: November 30, 2010
Results First Received: November 1, 2012
Last Updated: January 20, 2014
Health Authority: China: Ethics Committee

Keywords provided by Merck KGaA:
Hypertension
Bisoprolol
Atenolol

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Atenolol
Bisoprolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014