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

Overview[ - collapse ][ - ]

Purpose This is a multi-centre, randomized, open-label parallel trial to demonstrate the superiority and/or non-inferiority of bisoprolol on metoprolol succinate sustained-release (SR)
ConditionHypertension
InterventionDrug: Bisoprolol
Drug: Metoprolol
PhasePhase 4
SponsorMerck KGaA
Responsible PartyMerck KGaA
ClinicalTrials.gov IdentifierNCT01508325
First ReceivedJanuary 9, 2012
Last UpdatedFebruary 10, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateJanuary 9, 2012
Last Updated DateFebruary 10, 2014
Start DateDecember 2011
Estimated Primary Completion DateMarch 2014
Current Primary Outcome Measures
  • Change of mean ambulatory diastolic blood pressure in the last 4 hours after 12-week treatment from baseline (i.e. △DBP) [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean heart rate in the last 4 hours after 12-week treatment from baseline (i.e.△HR) [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures
  • Change of mean ambulatory systolic blood pressure baseline in the last 4 h (i.e. △SBP) [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean ambulatory 24-h blood pressure [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean ambulatory daytime blood pressure [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean ambulatory night-time blood pressure [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean ambulatory daytime heart rate [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • Change of mean ambulatory night-time heart rate [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]
  • 24-hour variability of blood pressure [Time Frame: 12 weeks] [Designated as safety issue: No]
  • The response rates for blood pressure [Time Frame: 12 weeks] [Designated as safety issue: No]DBP≤90 mmHg or a DBP reduction ≥10 mmHg from baseline
  • The response rates for heart rate [Time Frame: 12 weeks] [Designated as safety issue: No]10% HR reduction from baseline
  • Change of mean ambulatory 24-h heart rate [Time Frame: baseline and 12 weeks] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleComparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients
Official TitleComparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE Study)
Brief Summary
This is a multi-centre, randomized, open-label parallel trial to demonstrate the superiority
and/or non-inferiority of bisoprolol on metoprolol succinate sustained-release (SR)
Detailed Description
Primary objectives:

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

Secondary objectives:

1. To compare the efficacy of the 2 study drugs by 24h ambulatory monitoring by several
parameters at different times (e.g. blood pressure, heart rate, their variability,
etc...) after 12-week treatment from baseline among patients with mild to moderate
essential hypertension

2. To evaluate the safety of these two study drugs

3. To evaluate the compliance of the two study drugs
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care
ConditionHypertension
InterventionDrug: Bisoprolol
Dose escalation schedule: 5mg 1/d to 7.5mg 1/d to 10mg 1/d.
The active drug should be taken as close to 8am every morning. Every 4 weeks the dosage need to be up-titrated if the patient's blood pressure (BP) is ≥140 and/or 90mmHg. The first Ambulatory blood pressure monitoring (ABPM) is performed on the last day of the wash-out period. The second ABPM is performed on the last day of the active treatment.
Other Names:
ConcorDrug: Metoprolol
Dose escalation schedule: 47.5mg 1/d to 71.25mg 1/d to 95mg 1/d.
Comparison of different drug. Metoprolol succinate 47.5mg/tablet, oral
Study Arm (s)
  • Experimental: Bisoprolol Group
    Concor 5mg, oral
  • Active Comparator: Metoprolol SR Group
    Betaloc ZOK 47.5mg, oral

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment187
Estimated Completion DateMarch 2014
Estimated Primary Completion DateMarch 2014
Eligibility Criteria
Inclusion Criteria:

1. Patients aged: ≥18 years and ≤70 years old.

2. Essential hypertension (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 patients who have taken anti-hypertension drug.

3. Clinic resting Heart Rate (HR) ≥70bpm

4. Patients who have signed informed consent

Exclusion Criteria:

1. Patients with contraindications according to the China Summary of Product
Characteristics (SPCs) 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. Patients 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)
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesChina

Administrative Information[ + expand ][ + ]

NCT Number NCT01508325
Other Study ID NumbersEMR200006-520
Has Data Monitoring CommitteeNo
Information Provided ByMerck KGaA
Study SponsorMerck KGaA
CollaboratorsMerck Serono Co., Ltd., China
Investigators Study Director: Medical Director Merck Serono Co., Ltd., China
Verification DateFebruary 2014

Locations[ + expand ][ + ]

Merck Serono Investigational Site
Changsha City, China