Back to resultsComparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE)
Primary Purpose
Hypertension
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Bisoprolol
Metoprolol
Sponsored by
About this trial
This is an interventional supportive care trial for Hypertension focused on measuring Bisoprolol, Hypertension, Blood pressure, Heart rate
Eligibility Criteria
Inclusion Criteria:
- Subjects aged: >=18 years and =<70 years old
- 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.
- Clinic resting Heart Rate >=70 beats per minute (bpm)
- Patients who have signed informed consent
Exclusion Criteria:
- 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.
- Moderate EH patients who have used anti-hypertension drugs
- Secondary hypertension
- Subjects with history of coronary heart disease
- Chronic or acute heart failure
- Cerebrovascular events within 6 months before screening
- Impaired hepatic or renal function (according to local lab standard)
- Other protocol defined exclusion criteria could apply
Sites / Locations
- Merck Serono Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Bisoprolol
Metoprolol
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01508325
First Posted
January 9, 2012
Last Updated
April 28, 2015
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China
1. Study Identification
Unique Protocol Identification Number
NCT01508325
Brief Title
Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients
Acronym
CREATIVE
Official Title
Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE Study)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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:
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
To evaluate safety of the two drugs
To evaluate the treatment compliance of the two drugs
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Bisoprolol, Hypertension, Blood pressure, Heart rate
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
186 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bisoprolol
Arm Type
Experimental
Arm Title
Metoprolol
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Bisoprolol
Other Intervention Name(s)
Concor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Metoprolol
Other Intervention Name(s)
Betaloc SR
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment
Description
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
Title
Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment
Description
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 Outcome Measure Information:
Title
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment
Description
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
Title
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12
Description
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
Title
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12
Description
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
Title
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12
Description
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
Title
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12
Description
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
Title
Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12
Description
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
Title
Change From Baseline in 24-hour Blood Pressure Variability at Week 12
Description
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
Title
Blood Pressure Response Rate
Description
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
Title
Heart Rate Response Rate
Description
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
Title
Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects aged: >=18 years and =<70 years old
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.
Clinic resting Heart Rate >=70 beats per minute (bpm)
Patients who have signed informed consent
Exclusion Criteria:
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.
Moderate EH patients who have used anti-hypertension drugs
Secondary hypertension
Subjects with history of coronary heart disease
Chronic or acute heart failure
Cerebrovascular events within 6 months before screening
Impaired hepatic or renal function (according to local lab standard)
Other protocol defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Serono Co., Ltd., China
Official's Role
Study Director
Facility Information:
Facility Name
Merck Serono Investigational Site
City
Changsha City
Country
China
12. IPD Sharing Statement
Learn more about this trial
Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients
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