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

Phase 4

Completed

Conditions: Hypertension

Interventions: Drug: Bisoprolol
Drug: Metoprolol

Registration Number: NCT01508325

Lead Sponsor: Merck KGaA, Darmstadt, Germany

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:

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 186

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bisoprolol	Bisoprolol	-
Metoprolol	Metoprolol	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12	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 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 Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment	Baseline and 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 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	Baseline and 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	Baseline and 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	Baseline and 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 Night-time Heart Rate at Week 12	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 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	Baseline and 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.
Heart Rate Response Rate	Week 12	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	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 24 hours heart rate at Week 12 and of the baseline heart rate was calculated.
Blood Pressure Response Rate	Week 12	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.