Trial Outcomes & Findings for Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (NCT NCT01508325)

Last Updated: 2015-05-13

Results Overview

Ambulatory blood pressure monitoring (ABPM) determined blood pressure 3 times hourly in the daytime and once hourly in the nighttime. Only monitoring data with valid data greater than or equal to (\>=) 80 percent (%) was used for analysis. Each ABPM lasted for at least 24 hours. The first dynamic blood pressure monitoring was used as baseline. The difference between the mean ambulatory DBP observed in the last 4 hours after 12-week treatment and baseline was calculated to find out the change of mean ambulatory DBP at the end of the treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

186 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2015-05-13

Participant Flow

Participant milestones

Participant milestones
Measure	Bisoprolol Subjects received bisoprolol fumarate (Concor®) at a dose of 5 milligram (mg) once daily orally as sustained release (SR) tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic systolic blood pressure (SBP) was greater than or equal to (\>=) 140 millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) was \>=90 mmHg measured every 4 weeks.	Metoprolol Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Overall Study STARTED	93	93
Overall Study COMPLETED	75	72
Overall Study NOT COMPLETED	18	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Bisoprolol Subjects received bisoprolol fumarate (Concor®) at a dose of 5 milligram (mg) once daily orally as sustained release (SR) tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic systolic blood pressure (SBP) was greater than or equal to (\>=) 140 millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) was \>=90 mmHg measured every 4 weeks.	Metoprolol Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Overall Study Withdrawal by Subject	8	9
Overall Study Protocol Violation	0	3
Overall Study Physician Decision	2	1
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	5	6
Overall Study Other	2	2

Baseline Characteristics

Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Total n=186 Participants Total of all reporting groups
Age, Continuous	51.10 years STANDARD_DEVIATION 10.77 • n=5 Participants	49.89 years STANDARD_DEVIATION 10.46 • n=7 Participants	50.49 years STANDARD_DEVIATION 10.60 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	56 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	37 Participants n=7 Participants	94 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all the randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment Baseline (n=92, 93)	85.28 mmHg Standard Deviation 10.26	85.68 mmHg Standard Deviation 11.59
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment Change at Week 12 (n=65, 66)	-4.45 mmHg Standard Deviation 10.74	-3.39 mmHg Standard Deviation 11.23

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

Pulse rate was measured by palpation on radial artery for 1 minute. Two measurements were made at least 1 to 2 minutes apart. Finally mean heart rate was recorded. The first measured heart rate was used as baseline heart rate. The difference between the last 4 hours heart rate after 12-week treatment and of the baseline heart rate was calculated to measure the change in mean heart rate at the end of the treatment.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment Baseline (n=92, 93)	75.67 beats/min Standard Deviation 10.58	73.99 beats/min Standard Deviation 9.90
Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment Change at Week 12 (n=65, 66)	-8.04 beats/min Standard Deviation 12.65	-4.75 beats/min Standard Deviation 11.34

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

The ABPM determined blood pressure 3 times hourly in the daytime and once hourly in the nighttime. Only monitoring data with valid data \>=80% was used for analysis. Each ABPM lasted for at least 24 hours. The first dynamic blood pressure monitoring was used as baseline. The difference between the mean ambulatory SBP observed in the last 4 hours after 12-week treatment and baseline was calculated to find out the change of mean ambulatory SBP at the end of the treatment.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment Baseline (n=92, 93)	132.68 mmHg Standard Deviation 15.96	133.24 mmHg Standard Deviation 16.69
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment Change at Week 12 (n=65, 66)	-5.97 mmHg Standard Deviation 16.63	-5.12 mmHg Standard Deviation 15.12

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

The ABPM determined blood pressure 3 times hourly in the daytime and once hourly in the nighttime. Only monitoring data with valid data \>=80% was used for analysis. Each ABPM lasted for at least 24 hours. The first dynamic blood pressure monitoring was used as baseline. The difference between the mean ABPM observed in the last 24 hours at Week 12 and baseline was calculated to find out the change of mean ABPM at the end of the treatment.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12 SBP: Baseline (n=92, 93)	132.76 mmHg Standard Deviation 12.88	135.43 mmHg Standard Deviation 15.19
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12 SBP: Change at Week 12 (n=68, 67)	-5.40 mmHg Standard Deviation 14.59	-4.54 mmHg Standard Deviation 11.47
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12 DBP: Baseline (n=92, 93)	84.60 mmHg Standard Deviation 8.22	86.94 mmHg Standard Deviation 10.32
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12 DBP: Change at Week 12 (n=68, 67)	-4.58 mmHg Standard Deviation 9.01	-3.78 mmHg Standard Deviation 8.00

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

The ABPM determined blood pressure 3 times hourly in the daytime. Only monitoring data with valid data \>=80% was used for analysis. Each ABPM lasted for at least 24 hours. The first dynamic daytime blood pressure monitoring was used as baseline. The difference between the mean ambulatory daytime blood pressure observed at Week 12 and baseline was calculated to find out the change of mean ambulatory daytime blood pressure at the end of the treatment. Daytime in this study was defined as time between 06:00 am to 10:00 pm.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12 SBP: Baseline (n=92, 93)	135.40 mmHg Standard Deviation 13.11	138.31 mmHg Standard Deviation 15.09
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12 SBP: Change at Week 12 (n=68, 67)	-5.87 mmHg Standard Deviation 15.29	-5.16 mmHg Standard Deviation 12.11
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12 DBP: Baseline (n=92, 93)	86.43 mmHg Standard Deviation 8.88	88.86 mmHg Standard Deviation 10.58
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12 DBP: Change at Week 12 (n=68, 67)	-4.76 mmHg Standard Deviation 9.34	-3.82 mmHg Standard Deviation 8.69

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

The ABPM determined blood pressure once hourly in the nighttime. Only monitoring data with valid data \>=80% was used for analysis. Each ABPM lasted for at least 24 hours. The first nighttime blood pressure monitoring was used as baseline. The difference between the mean ambulatory nighttime blood pressure observed at Week 12 and baseline was calculated to find out the change of mean ambulatory nighttime blood pressure at the end of the treatment. Nighttime in this study was defined as 10:00 pm to 06:00 am.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12 SBP: Baseline (n=92, 93)	125.16 mmHg Standard Deviation 14.14	127.15 mmHg Standard Deviation 16.99
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12 SBP: Change at Week 12 (n=68, 66)	-4.81 mmHg Standard Deviation 14.31	-2.65 mmHg Standard Deviation 14.23
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12 DBP: Baseline (n=92, 93)	79.14 mmHg Standard Deviation 7.68	81.19 mmHg Standard Deviation 11.89
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12 DBP: Change at Week 12 (n=68, 66)	-5.08 mmHg Standard Deviation 9.29	-3.39 mmHg Standard Deviation 8.76

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

Pulse rate was measured by palpation on radial artery for 1 minute. Two measurements were made at least 1 to 2 minutes apart. Finally mean heart rate was recorded. The first measured daytime heart rate was used as baseline heart rate. The difference between the daytime heart rate at Week 12 treatment and of the baseline heart rate was calculated to measure the change of mean ambulatory daytime heart rate at the end of the treatment. Daytime in this study was defined as 06:00 am to 10:00 pm.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12 Baseline (n=92, 93)	80.66 beats/min Standard Deviation 8.85	78.94 beats/min Standard Deviation 8.04
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12 Change at Week 12 (n=66, 67)	-9.60 beats/min Standard Deviation 10.76	-3.85 beats/min Standard Deviation 9.21

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

Pulse rate was measured by palpation on radial artery for 1 minute. Two measurements were made at least 1 to 2 minutes apart. Finally mean heart rate was recorded. The first measured heart rate was used as baseline heart rate. The difference between the nighttime heart rate at Week 12 treatment and of the baseline heart rate was calculated to measure the change of mean ambulatory nighttime heart rate at the end of the treatment. Nighttime was defined as 10:00 pm to 06:00 am.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12 Baseline (n=92, 93)	67.73 beats/min Standard Deviation 8.26	66.85 beats/min Standard Deviation 7.38
Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12 Change at Week 12 (n=66, 66)	-4.72 beats/min Standard Deviation 9.90	-1.50 beats/min Standard Deviation 7.24

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

The ABPM determined blood pressure 3 times hourly in the daytime and once hourly in the nighttime. Only monitoring data with valid data \>=80% was used for analysis. Each ABPM lasted for at least 24 hours. The first dynamic blood pressure monitoring was used as baseline. The mean change in the blood pressure variability between the 24-hour blood pressure observed at Week 12 and baseline was calculated.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in 24-hour Blood Pressure Variability at Week 12 SBP variability: Baseline (n=91, 92)	10.89 mmHg Standard Deviation 3.45	10.45 mmHg Standard Deviation 2.33
Change From Baseline in 24-hour Blood Pressure Variability at Week 12 SBP variability: Change at Week 12 (n=66, 66)	-0.12 mmHg Standard Deviation 3.56	0.09 mmHg Standard Deviation 3.05
Change From Baseline in 24-hour Blood Pressure Variability at Week 12 DBP variability: Baseline (n=91, 92)	12.68 mmHg Standard Deviation 3.63	12.09 mmHg Standard Deviation 3.02
Change From Baseline in 24-hour Blood Pressure Variability at Week 12 DBP variability: Change at Week 12 (n=66, 66)	0.02 mmHg Standard Deviation 3.54	0.76 mmHg Standard Deviation 3.30

SECONDARY outcome

Timeframe: Week 12

Population: ITT analysis population included all randomized subjects. 'N' (number of subjects analyzed) signifies number of evaluable subjects for this outcome measure.

Blood pressure response was defined as DBP less than or equal to (=\<) 90 mmHg or \>=10 mmHg decrease in DBP from baseline. Blood pressure response rate was calculated as: number of subjects with blood pressure response divided by total number of subjects and multiplied by 100.

Outcome measures

Outcome measures
Measure	Bisoprolol n=75 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=72 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Blood Pressure Response Rate	86.67 percentage of subjects	83.33 percentage of subjects

SECONDARY outcome

Timeframe: Week 12

Population: ITT analysis population included all randomized subjects. 'N' (number of subjects analyzed) signifies number of evaluable subjects for this outcome measure.

Heart rate response was defined as decrease in heart rate from baseline \>=10 percent (%). Heart rate response rate was calculated by using the number of subjects with heart rate response divided by total number of subjects and multiplied by 100.

Outcome measures

Outcome measures
Measure	Bisoprolol n=75 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=72 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Heart Rate Response Rate	72.00 percentage of subjects	55.56 percentage of subjects

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT analysis population included all randomized subjects. 'n' signifies number of subjects evaluable for this outcome measure at given timepoints for each group, respectively.

Outcome measures

Outcome measures
Measure	Bisoprolol n=93 Participants Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 Participants Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12 Baseline (n=92, 93)	77.45 beats/min Standard Deviation 8.42	75.80 beats/min Standard Deviation 7.53
Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12 Change at Week 12 (n=67, 67)	-8.46 beats/min Standard Deviation 10.43	-3.24 beats/min Standard Deviation 8.03

Adverse Events

Bisoprolol

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Metoprolol

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bisoprolol n=93 participants at risk Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 participants at risk Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Nervous system disorders Dizziness	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Nervous system disorders Transient attack	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Bisoprolol n=93 participants at risk Subjects received bisoprolol fumarate (Concor®) at a dose of 5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of bisoprolol was escalated to 7.5 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 10 mg orally once daily for the next 4 weeks (Weeks 8 to 12), if clinic SBP was \>= 140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.	Metoprolol n=93 participants at risk Subjects received metoprolol succinate (Betaloc SR) at a dose of 47.5 mg once daily orally as SR tablets for a period of 4 weeks. The dose of metoprolol was escalated to 71.25 mg orally once daily for next 4 weeks (Weeks 4 to 8) and to 95 mg orally once daily for the next 4 weeks (Weeks 8 to 12) if clinic SBP was \>=140 mmHg and/or DBP was \>=90 mmHg measured every 4 weeks.
Cardiac disorders Angina	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Cardiac disorders Bradycardia	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Cardiac disorders Coronary artery disease	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Cardiac disorders Myocardial ischemia	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Cardiac disorders Palpitation	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Cardiac disorders Ventricular premature contraction	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Gastrointestinal disorders Abdominal discomfort	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Gastrointestinal disorders Constipation	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
General disorders Fatigue	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
General disorders Chest discomfort	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Infections and infestations Nasopharyngitis	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Infections and infestations Urinary tract infection	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High alanine aminotransferase	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High serum cholesterol level	3.2% 3/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High blood glucose	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High blood triglycerides level	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	4.3% 4/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High serum uric acid level	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations Low high-density lipoprotein level	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations High low-density lipoprotein level	4.3% 4/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	3.2% 3/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations Urine leucocyte (positive)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Investigations Urine protein (positive)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Metabolism and nutrition disorders Loss of appetite	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Nervous system disorders Dizziness	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Nervous system disorders Headache	2.2% 2/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Nervous system disorders Somnolence	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Respiratory, thoracic and mediastinal disorders Asthma	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)
Skin and subcutaneous tissue disorders Rash	0.00% 0/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)	1.1% 1/93 • From the first administration of the trial medication up to the end of the treatment (12 weeks)