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
Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT01251146
Collaborator
Merck Serono Co., Ltd., China (Industry)
177
2
2
15
88.5
5.9
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
177 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date
:
Nov 1, 2010
Actual Primary Completion Date
:
Feb 1, 2012
Actual Study Completion Date
:
Feb 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal [Baseline and attainment of heart rate goal (Week 2 or Week 4 or Week 6)]
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 [Baseline and end of follow-up (Week 4 or Week 6 or Week 8)]
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 [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)]
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 [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)]
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 [Baseline up to attainment of heart rate goal (Week 2 or Week 4 or Week 6)]
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 [Attainment of heart rate goal (Week 2 or Week 4 or Week 6)]
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) [Baseline up to end of follow-up (Week 4 or Week 6 or Week 8)]
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 [Baseline up to end of follow-up (Week 4 or Week 6 or Week 8)]
Participants compliant with study treatment were the participants who have completed the study treatment regimen.
Eligibility Criteria
Criteria
Ages Eligible for Study:
25 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Shi Jingshan Hospital | Beijing | China | ||
| 2 | Shanghai Institute of Hypertension | Shanghai | China |
Sponsors and Collaborators
- Merck KGaA, Darmstadt, Germany
- Merck Serono Co., Ltd., China
Investigators
- Principal Investigator: Gao Pingjin, Prof., Shanghai Institute of Hypertension
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT01251146
Other Study ID Numbers:
- EMR200006-515
First Posted:
Dec 1, 2010
Last Update Posted:
Mar 8, 2017
Last Verified:
Jan 1, 2017
Keywords provided by Merck KGaA, Darmstadt, Germany
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Period Title: Overall Study | ||
| STARTED | 86 | 91 |
| COMPLETED | 83 | 81 |
| NOT COMPLETED | 3 | 10 |
Baseline Characteristics
| Arm/Group Title | Bisoprolol | Atenolol | Total |
|---|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Total of all reporting groups |
| Overall Participants | 86 | 91 | 177 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
45.44
(9.78)
|
46.30
(9.87)
|
45.88
(9.81)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
31
36%
|
38
41.8%
|
69
39%
|
| Male |
55
64%
|
53
58.2%
|
108
61%
|
Outcome Measures
| Title | Change From Baseline in Baroreflex Sensitivity (BRS) at Attainment of Heart Rate Goal |
|---|---|
| Description | 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). |
| Time Frame | Baseline and attainment of heart rate goal (Week 2 or Week 4 or Week 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population included all randomized participants who received at least 1 dose of study medication. "N" signifies those participants who were evaluated for this measure. "n" signifies those participants who were evaluated for this measure at the specified time point for each treatment arm group respectively. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 75 | 79 |
| Baseline (n=75,79) |
7.78
(2.92)
|
7.92
(3.26)
|
| Change at attainment of heart rate goal (n=67,66) |
3.27
(3.67)
|
2.88
(4.05)
|
| Title | Change From Baseline in Baroreflex Sensitivity (BRS) at End of Follow-up |
|---|---|
| Description | 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. |
| Time Frame | Baseline and end of follow-up (Week 4 or Week 6 or Week 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. "N" signifies those participants who were evaluated for this measure. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 71 | 66 |
| Mean (Standard Deviation) [millisecond per millimeter of mercury] |
4.08
(3.79)
|
3.31
(3.83)
|
| Title | 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 |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. "N" signifies those participants who were evaluated for this measure. "n" signifies those participants who were evaluated for this measure at the specified time point for each treatment arm group respectively. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 75 | 79 |
| HRV for LF at Baseline (n=75,79) |
261.80
(208.40)
|
322.09
(315.30)
|
| Change for LF: heart rate goal (n=71,71) |
90.04
(352.97)
|
26.14
(416.51)
|
| Change at end of follow-up for LF (n=71,66) |
89.40
(330.26)
|
-22.00
(295.54)
|
| HRV for HF at Baseline (n=75,79) |
171.26
(161.43)
|
193.48
(216.06)
|
| Change for HF: heart rate goal (n=71,71) |
148.91
(338.13)
|
136.67
(314.47)
|
| Change at end of follow-up for HF (n=71,66) |
186.46
(288.53)
|
178.05
(375.70)
|
| Title | 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 |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. "N" signifies those participants who were evaluated for this measure. "n" signifies those participants who were evaluated for this measure at the specified time point for each treatment arm group respectively. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 75 | 79 |
| Baseline (n=75,79) |
2.16
(1.89)
|
2.40
(1.96)
|
| Change at attainment of heart rate goal (n=71,71) |
-0.70
(1.76)
|
-0.90
(1.62)
|
| Change at end of follow-up (n=71,66) |
-0.69
(2.08)
|
-1.15
(1.68)
|
| Title | Number of Participants Attaining Heart Rate Goal at Dosage 1, 2 and 3 of Study Treatment |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to attainment of heart rate goal (Week 2 or Week 4 or Week 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 86 | 91 |
| Dosage 1 |
72
83.7%
|
72
79.1%
|
| Dosage 2 |
7
8.1%
|
6
6.6%
|
| Dosage 3 |
1
1.2%
|
0
0%
|
| Title | Percentage of Participants Attaining Heart Rate Goal at Week 2, 4 and 6 |
|---|---|
| Description | Heart rate goal was defined as attainment of heart rate less than or equal to 65 bpm. |
| Time Frame | Attainment of heart rate goal (Week 2 or Week 4 or Week 6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 86 | 91 |
| Week 2 |
83.72
97.3%
|
79.12
86.9%
|
| Week 4 |
91.86
106.8%
|
85.71
94.2%
|
| Week 6 |
93.02
108.2%
|
85.71
94.2%
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 86 | 91 |
| Number of participants with AEs |
6
7%
|
6
6.6%
|
| Number of participants with SAEs |
0
0%
|
0
0%
|
| Title | Number of Participants Compliant With Study Treatment |
|---|---|
| Description | Participants compliant with study treatment were the participants who have completed the study treatment regimen. |
| Time Frame | Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all randomized participants who received at least 1 dose of study medication. |
| Arm/Group Title | Bisoprolol | Atenolol |
|---|---|---|
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. |
| Measure Participants | 86 | 91 |
| Number [participants] |
83
96.5%
|
81
89%
|
Adverse Events
| Time Frame | Baseline up to end of follow-up (Week 4 or Week 6 or Week 8) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Bisoprolol | Atenolol | ||
| Arm/Group Description | Bisoprolol was administered at a dose of 5 milligram (mg) once daily for 2 weeks. If the heart rate was less than or equal to 65 beats per minute (bpm) at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 7.5 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate was still greater than 65 bpm at Week 4, then the dose was further increased to 10 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose was administered for another 2 weeks (up to Week 8). If the heart rate was still greater than 65 bpm, then the treatment was ceased. | Atenolol was administered at a dose of 50 mg once daily for 2 weeks. If the heart rate was less than or equal to 65 bpm at Week 2, then the initial dose was administered for another 2 weeks (up to Week 4). If the heart rate was greater than 65 bpm at Week 2, then the dose was further increased to 75 mg once daily for 2 weeks (up to Week 4). If the heart rate was less than or equal to 65 bpm at Week 4, the increased dose was administered for another 2 weeks (up to Week 6). If the heart rate still greater than 65 bpm at Week 4, then the dose was further increased to 100 mg once daily for 2 weeks (up to Week 6). If the heart rate was less than or equal to 65 bpm at Week 6, the increased dose administered for another 2 weeks. If the heart rate was still greater than 65 bpm, then the treatment was ceased. | ||
All Cause Mortality |
||||
| Bisoprolol | Atenolol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bisoprolol | Atenolol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/86 (0%) | 0/91 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bisoprolol | Atenolol | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/86 (7%) | 6/91 (6.6%) | ||
| Cardiac disorders | ||||
| Bradycardia | 0/86 (0%) | 1/91 (1.1%) | ||
| General disorders | ||||
| Chest distress | 0/86 (0%) | 1/91 (1.1%) | ||
| Metabolism and nutrition disorders | ||||
| Elevated Triglyceride | 4/86 (4.7%) | 4/91 (4.4%) | ||
| Elevated Cholesterol | 2/86 (2.3%) | 0/91 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 0/86 (0%) | 2/91 (2.2%) | ||
| Headache | 0/86 (0%) | 1/91 (1.1%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Merck KGaA Communication Center |
|---|---|
| Organization | Merck Serono, a division of Merck KGaA |
| Phone | +49-6151-72-5200 |
| service@merckgroup.com |
Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT01251146
Other Study ID Numbers:
- EMR200006-515
First Posted:
Dec 1, 2010
Last Update Posted:
Mar 8, 2017
Last Verified:
Jan 1, 2017