HypertensionPhase 4CREATIVENCT01508325
Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients
A Phase 4 study testing Bisoprolol and Metoprolol in people with Hypertension, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Bisoprolol and Metoprolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 1 siteChina
- Study dates
- Dec 2011to Apr 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE Study)
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:
- 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
- Conditions
- Hypertension
- Being tested
- Bisoprolol, Metoprolol
- Keywords
- Bisoprolol, Hypertension, Blood pressure, Heart rate
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BisoprololDrug
Also called Concor
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.
MetoprololDrug
Also called Betaloc SR
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.
| Study group | Role | What they receive |
|---|---|---|
| Bisoprolol | Experimental | Not described Receives: Drug: Bisoprolol |
| Metoprolol | Active comparator | Not described Receives: Drug: Metoprolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
Secondary outcomes (10)
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Baseline and Week 12
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.
Measured: Week 12
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.
Measured: Week 12
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.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2012 (estimated)
- Study startDec 2011
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Serono Co., Ltd., China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01508325
- Sponsor's protocol ID
- EMR200006-520
- Acronym
- CREATIVE
- Status last verified
- Apr 2015
- First submitted
- 9 Jan 2012
- Last updated
- 13 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE Study)
- ClinicalTrials.gov ID
- NCT01508325
- Acronym / sponsor ID
- CREATIVE / EMR200006-520
- Conditions
- Hypertension
- Keywords
- Bisoprolol, Hypertension, Blood pressure, Heart rate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Study start
- Dec 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 11 Jan 2012 (estimated)
- Results
- Posted 13 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bisoprolol | Experimental | Drug: Bisoprolol |
| Metoprolol | Active comparator | Drug: Metoprolol |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BisoprololAlso: ConcorSubjects 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. | Drug | Bisoprolol |
| MetoprololAlso: Betaloc SRSubjects 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. | Drug | Metoprolol |
Primary outcome
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment
Time frame: Baseline and Week 12
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
Time frame: Baseline and 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 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.
10 secondary outcomes
Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment
Time frame: Baseline and Week 12
Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12
Time frame: Baseline and Week 12
Change From Baseline in 24-hour Blood Pressure Variability at Week 12
Time frame: Baseline and Week 12
Blood Pressure Response Rate
Time frame: Week 12
Heart Rate Response Rate
Time frame: Week 12
Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Serono Co., Ltd., China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bisoprolol and Metoprolol in people with Hypertension, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2015.