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CompletedNCT01508325CREATIVEUpdated May 13, 2015Results posted

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

A Phase 4 interventional study of Bisoprolol and Metoprolol in Hypertension, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2015-05-13.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 4, Interventional, and Supportive care

Phase
Phase 4
Study type
Interventional
Enrollment
186
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

This is a multicentre, randomized, open-label parallel trial to demonstrate the superiority and/or non-inferiority of bisoprolol on metoprolol succinate sustained-release (SR) tablet in subjects with mild to moderate primary hypertension.

Read the detailed description

Primary objectives:

To demonstrate that bisoprolol is superior in mean ambulatory heart rate and/or non-inferior in mean ambulatory DBP as compared with metoprolol SR in the last 4 hours after 12-week active treatment in subjects with mild to moderate essential hypertension (EH).

Secondary objectives:

  1. To compare the efficacy of the 2 study drugs by 24h ambulatory monitoring by several parameters at different times (Example: blood pressure, heart rate, their variability, etc...) after 12-week treatment from baseline among subjects with mild to moderate EH
  2. To evaluate safety of the two drugs
  3. To evaluate the treatment compliance of the two drugs
02

Conditions studied

  • Hypertension

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Keywords

  • Bisoprolol
  • Hypertension
  • Blood pressure
  • Heart rate
03

In context

Hypertension

6,687 studies on the registry are indexed under Hypertension; 964 are open to participants now.

This study's enrollment of 186 is above the median of 90 across 4,994 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

Merck KGaA, Darmstadt, Germany is the lead sponsor of 269 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Subjects aged: >=18 years and =\<70 years old
  2. EH who are suitable for mono-therapy, either mild to moderate EH patients who have not been treated with anti-hypertension drugs, or mild EH subjects who have taken anti-hypertension drug.
  3. Clinic resting Heart Rate >=70 beats per minute (bpm)
  4. Patients who have signed informed consent

Exclusion criteria

Exclusion Criteria:

  1. Subjects with contraindications according to the China Summary of Product Characteristics (SmPCs) of both bisoprolol and metoprolol SR, such as acute heart failure, second or third degree atrioventricular block (without a pacemaker), sick sinus syndrome, symptomatic bradycardia or symptomatic hypotension, severe bronchial asthma or severe chronic obstructive pulmonary disease, metabolic acidosis, etc.
  2. Moderate EH patients who have used anti-hypertension drugs
  3. Secondary hypertension
  4. Subjects with history of coronary heart disease
  5. Chronic or acute heart failure
  6. Cerebrovascular events within 6 months before screening
  7. Impaired hepatic or renal function (according to local lab standard)
  8. Other protocol defined exclusion criteria could apply
05

Study design

Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
186 participants (actual)

Study arms

  • Experimental
    Bisoprolol

    Drug: Bisoprolol

  • Active comparator
    Metoprolol

    Drug: Metoprolol

Interventions

  • DrugBisoprolol

    Subjects will receive 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 will be 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.

    Also known as: Concor

  • DrugMetoprolol

    Subjects will receive 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 will be 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.

    Also known as: Betaloc SR

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment

    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.

    Time frame: Baseline and Week 12

  2. Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment

    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.

    Time frame: Baseline and Week 12

Secondary outcomes

  1. Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment

    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.

    Time frame: Baseline and Week 12

  2. Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12

    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.

    Time frame: Baseline and Week 12

  3. Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12

    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.

    Time frame: Baseline and Week 12

  4. Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12

    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.

    Time frame: Baseline and Week 12

  5. Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12

    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.

    Time frame: Baseline and Week 12

  6. Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12

    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.

    Time frame: Baseline and Week 12

  7. Change From Baseline in 24-hour Blood Pressure Variability at Week 12

    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.

    Time frame: Baseline and Week 12

  8. Blood Pressure Response Rate

    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.

    Time frame: Week 12

  9. Heart Rate Response Rate

    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.

    Time frame: Week 12

  10. Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12

    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 24 hours heart rate at Week 12 and of the baseline heart rate was calculated.

    Time frame: Baseline and Week 12

07

Results

Posted May 13, 2015

Participant flow

Participant flow — Overall Study
MilestoneBisoprololMetoprolol
Started9393
Completed7572
Not completed1821
Withdrew: Withdrawal by subject89
Withdrew: Protocol violation03
Withdrew: Physician decision21
Withdrew: Adverse event10
Withdrew: Lost to follow-up56
Withdrew: Other22

Outcome measures

PrimaryChange From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment
mmHgBisoprololMetoprolol
Baseline (n=92, 93)85.28 ± 10.2685.68 ± 11.59
Change at Week 12 (n=65, 66)-4.45 ± 10.74-3.39 ± 11.23
PrimaryChange From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · beats/min
Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment
beats/minBisoprololMetoprolol
Baseline (n=92, 93)75.67 ± 10.5873.99 ± 9.90
Change at Week 12 (n=65, 66)-8.04 ± 12.65-4.75 ± 11.34
SecondaryChange From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment
mmHgBisoprololMetoprolol
Baseline (n=92, 93)132.68 ± 15.96133.24 ± 16.69
Change at Week 12 (n=65, 66)-5.97 ± 16.63-5.12 ± 15.12
SecondaryChange From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12
mmHgBisoprololMetoprolol
SBP: Baseline (n=92, 93)132.76 ± 12.88135.43 ± 15.19
SBP: Change at Week 12 (n=68, 67)-5.40 ± 14.59-4.54 ± 11.47
DBP: Baseline (n=92, 93)84.60 ± 8.2286.94 ± 10.32
DBP: Change at Week 12 (n=68, 67)-4.58 ± 9.01-3.78 ± 8.00
SecondaryChange From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12
mmHgBisoprololMetoprolol
SBP: Baseline (n=92, 93)135.40 ± 13.11138.31 ± 15.09
SBP: Change at Week 12 (n=68, 67)-5.87 ± 15.29-5.16 ± 12.11
DBP: Baseline (n=92, 93)86.43 ± 8.8888.86 ± 10.58
DBP: Change at Week 12 (n=68, 67)-4.76 ± 9.34-3.82 ± 8.69
SecondaryChange From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12
mmHgBisoprololMetoprolol
SBP: Baseline (n=92, 93)125.16 ± 14.14127.15 ± 16.99
SBP: Change at Week 12 (n=68, 66)-4.81 ± 14.31-2.65 ± 14.23
DBP: Baseline (n=92, 93)79.14 ± 7.6881.19 ± 11.89
DBP: Change at Week 12 (n=68, 66)-5.08 ± 9.29-3.39 ± 8.76
SecondaryChange From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · beats/min
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12
beats/minBisoprololMetoprolol
Baseline (n=92, 93)80.66 ± 8.8578.94 ± 8.04
Change at Week 12 (n=66, 67)-9.60 ± 10.76-3.85 ± 9.21
SecondaryChange From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · beats/min
Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12
beats/minBisoprololMetoprolol
Baseline (n=92, 93)67.73 ± 8.2666.85 ± 7.38
Change at Week 12 (n=66, 66)-4.72 ± 9.90-1.50 ± 7.24
SecondaryChange From Baseline in 24-hour Blood Pressure Variability at Week 12

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.

Time frame:
Baseline and Week 12
Reported as:
Mean · mmHg
Change From Baseline in 24-hour Blood Pressure Variability at Week 12
mmHgBisoprololMetoprolol
SBP variability: Baseline (n=91, 92)10.89 ± 3.4510.45 ± 2.33
SBP variability: Change at Week 12 (n=66, 66)-0.12 ± 3.560.09 ± 3.05
DBP variability: Baseline (n=91, 92)12.68 ± 3.6312.09 ± 3.02
DBP variability: Change at Week 12 (n=66, 66)0.02 ± 3.540.76 ± 3.30
SecondaryBlood Pressure Response Rate

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.

Time frame:
Week 12
Reported as:
Number · percentage of subjects
Blood Pressure Response Rate
percentage of subjectsBisoprololMetoprolol
Blood Pressure Response Rate86.6783.33
SecondaryHeart Rate Response Rate

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.

Time frame:
Week 12
Reported as:
Number · percentage of subjects
Heart Rate Response Rate
percentage of subjectsBisoprololMetoprolol
Heart Rate Response Rate72.0055.56
SecondaryChange From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12

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 24 hours heart rate at Week 12 and of the baseline heart rate was calculated.

Time frame:
Baseline and Week 12
Reported as:
Mean · beats/min
Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12
beats/minBisoprololMetoprolol
Baseline (n=92, 93)77.45 ± 8.4275.80 ± 7.53
Change at Week 12 (n=67, 67)-8.46 ± 10.43-3.24 ± 8.03

Adverse events

Collected over From the first administration of the trial medication up to the end of the treatment (12 weeks). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Bisoprolol—2/93 (2.2%)17/93 (18.3%)
Metoprolol—0/93 (0%)16/93 (17.2%)
Most frequent serious events
Most frequent serious events
EventBisoprololMetoprolol
DizzinessNervous system disorders1/930/93
Transient attackNervous system disorders1/930/93
Most frequent other events
Showing 10 of 28
Most frequent other events
EventBisoprololMetoprolol
High blood triglycerides levelInvestigations2/934/93
High low-density lipoprotein levelInvestigations4/933/93
High serum cholesterol levelInvestigations3/932/93
PalpitationCardiac disorders1/932/93
Chest discomfortGeneral disorders0/932/93
High serum uric acid levelInvestigations0/932/93
DizzinessNervous system disorders2/932/93
HeadacheNervous system disorders2/930/93
AnginaCardiac disorders1/930/93
BradycardiaCardiac disorders1/930/93

Baseline characteristics

Intention-to-treat (ITT) analysis population included all randomized subjects.

Age, Continuous
Age, Continuous(years)BisoprololMetoprololTotal
Mean51.10 ± 10.7749.89 ± 10.4650.49 ± 10.60
Sex: Female, Male
Sex: Female, Male(Participants)BisoprololMetoprololTotal
Female365692
Male573794
08

Study locations

1 site
  • Merck Serono Investigational Site
    Changsha City, China
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 13, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01508325
Lead sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China
Responsible party
Sponsor
First posted
Jan 11, 2012
Start date
Dec 2011
Primary completion
Apr 2014
Completion
Apr 2014
Results posted
May 13, 2015
Last update
May 13, 2015

Study contacts

Medical Director
study director · Merck Serono Co., Ltd., China

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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