Biso-CHF: Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03026088
• Collaborator: Merck Serono Co., Ltd., China (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 21.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a single-arm, open label, interventional, multi-center, phase 4 pilot study.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Bisoprolol	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-arm, Interventional, Multi-center, Pilot Study to Evaluate the Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Patients With NYHA Class II - IV (Biso-CHF Study)
• Actual Study Start Date: Mar 21, 2017
• Actual Primary Completion Date: Dec 26, 2018
• Actual Study Completion Date: Dec 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bisoprolol	Drug: Bisoprolol; Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.; Other Names: Brand name: Concor

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Resting Heart Rate at Week 6 [Baseline, Week 6]

   Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

2. Change From Baseline in Resting Heart Rate at Week 14 [Baseline, Week 14]

   Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

3. Change From Baseline in Resting Heart Rate at Week 26 [Baseline, Week 26]

   Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Secondary Outcome Measures

1. Change From Baseline in Resting Heart Rate at Week 3, 10 and 18 [Baseline, Week 3, 10 and 18]

   Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

2. Left Ventricular Ejection Fraction (LVEF) at Baseline, Week 14 and 26 [Baseline, Week 14 and 26]

   LVEF was defined as the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat and it is used to measure the cardiac output for the heart. Ultrasound cardiogram performed to measure LVEF.

3. Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26 [Baseline, Week 14 and 26]

   Left Ventricular End-Systolic Dimension was measured by Ultrasound cardiogram.

4. Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26 [Baseline, Week 14 and 26]

   Left Ventricular End-diastolic Dimension was measured by Ultrasound cardiogram.

5. Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26 [Baseline, Week 14 and 26]

   Interventricular septal thickness was measured by Ultrasound cardiogram.

6. Ratio of Early (E) to Late (A) Ventricular Filling Velocities (E/A Ratio) at Baseline, Week 14 and Week 26 [Baseline, Week 14 and Week 26]

   Early to late ratio was measured by ultrasound cardiogram.

7. Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure [Screening (Week -2) up to Week 26]

   Blood pressure (systolic and diastolic) measurement was taken at sitting position, with the elbow at the same level with the heart. Number of participants with clinically relevant systolic and diastolic blood pressure reported based on the assessment of the investigator.

8. Number of Participants With New York Heart Association (NYHA) Class [Baseline, Week 26]

   The NYHA classification assesses the severity of symptoms of heart failure. Here NYHA class of II - IV was assessed. NYHA II: Slight limitation of physical activity, comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue or palpitation. NYHA III: Marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes undue breathlessness, fatigue or palpitation. NYHA IV: Unable to carry on any physical activity without discomfort, symptoms at rest can be present. If any physical activity is undertaken, discomfort increased.

9. Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm [Baseline up to Week 26]

   Resting heart rate measurement was taken at sitting position for a continuous record of 3 minutes. Heartbeats in each minute was calculated and averaged to obtain the resting heart rate.

10. Quality of Life Based on Minnesota Living With Heart Failure (MLHF) at Baseline and End of Treatment [Baseline, end of treatment (Week 26)]

    MLHF questionnaire has 21 items. Questions assess the impact of frequent physical symptoms of heart failure and the effects of heart failure on physical and social functions. Each question had a possible score of 0 (best) to 5 (worst), for a total of 0 to 105. The higher the summed score, the worse is the impact of heart failure on a participant's quality of life.

11. Quality of Life Based on the Medical Outcomes Study Item Short From Health Survey (SF-36) at Baseline and End of Treatment [Baseline, end of treatment (Week 26)]

    Short Form Health Survey (SF-36), an instrument composed by 8 subscales: Physical Functioning, Physical Role Function, Bodily Pain, General Health, Vitality, Social Functioning, Emotional Role Function and Mental Health. The individual question items (Likert scale 0-4) are first summed for each item under the various sections. Then, those summary scores are then standardized on a scale between 0 and 1 using the mean and standard deviation of the actual scores and finally, weighted to a scale between 0 and 100. The items contributing to a scale are scored so that a higher score represents better health, and they are averaged together to create the scale score. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

12. 6-Minute Walk Test [Baseline and End of treatment (Week 26)]

    6-min walk test was a practical simple test that requires a 100-feet hallway but no exercise equipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired participants. This test measures the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.

13. Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP) [Baseline up to End of treatment (Week 26)]

    Routine blood tests was performed to measure NT Pro-BNP. The normal range for NT Pro-BNP varies from 0 picograms/milliliter (pg/mL) (lower limit of normal value) -125 pg/mL (upper limit of normal value).

14. Mean 24 Hour, Day Time and Night Time Heart Rate [Baseline, week 6, 14 and end of treatment (Week 26)]

    Holter monitor was used to measure heart rate (24 hour, day time, night time).

15. Number of Participants With Arrhythmia [Baseline up to end of treatment (Week 26)]

    Holter monitor was used to diagnose arrhythmia.

16. Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm [Baseline, week 6, 14 and end of treatment (Week 26)]

    Holter monitor was used to measure heart rate.

17. Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR) [Up to Week 26]

    MPR is used to assess the medicine compliance. MPR is defined as the actual drug number taken by the participants divided by the drug number should be taken by the participants according to the protocol. MPR between 80%-100% is defined as good compliance. Medication rate of less than (<) 80% or greater than (>)100% is defined as insufficient compliance.

18. Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure [Up to Week 26]

    Number of participants with all-cause mortality, cardiac death, or re-admission due to heart failure was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18-80 year, male or female.

• Chronic Heart failure subjects with medical history of cardiac disease or other related cardiovascular disease.

• Left ventricular ejection fraction (LVEF) less than or equal to (=<) 40 percent (%).

• New York Heart Association (NYHA) class of II - IV

• NYHA II ： Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue or palpitation.

• NYHA III：Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes undue breathlessness, fatigue or palpitation.

• NYHA IV：Unable to carry on any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort increased.

• Signed Informed Consent Form (ICF).

Exclusion Criteria:

• Acute coronary syndrome (ACS) within 3 months.

• Under beta-blocker treatment for the last 2 weeks.

• Under other medicine treatment which may affect heart rate, like Non-dihydropyridine calcium channel blockers (NDHP-CCBs) or ivabradine for the last 2 weeks; Under Digoxin treatment [more than (>) 0.125 milligram (mg)].

• Uncontrolled Diabetes [hemoglobin A1c, (HbA1c) >7.5%].

• Severe or uncontrolled hypertension [resting Systolic Blood Pressure (SBP) >180 millimeters of mercury (mmHg), or resting Diastolic Blood Pressure (DBP) >110mmHg at screening period].

• Severe hypotension [resting SBP less than (<) 90mmHg, or resting DBP<50mmHg].

• Resting heart rate <60 beat per minute (bpm).

• Any contradiction to Bisoprolol according to label, including:

• Acute heart failure or during episodes of heart failure decompensation requiring intravenous inotropic therapy.

• Cardiogenic shock.

• Atrioventricular block of second or third degree (without a pacemaker).

• Sick sinus syndrome.

• Sinoatrial block.

• Slowed heart rate, causing symptoms (symptomatic bradycardia),

• Decreased blood pressure, causing symptoms (symptomatic hypotension),

• Severe bronchial asthma or severe chronic obstructive pulmonary disease.

• Sever forms of peripheral arterial occlusive disease and Raynaud's syndrome.

• Untreated phaeochromocytoma.

• Metabolic acidosis.

• Hypersensitivity to bisoprolol or to any of the excipients.

• Severe Arrhythmia including atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter or ventricular tachycardia.

• Significant valvular heart disease, congenital heart disease, pulmonary heart disease or perinatal heart disease.

• Acute pulmonary edema.

• Severe hepatic dysfunction, defined as:

• Serum Alanine Aminotransferase (ALT) > triple the upper limit of the normal range; and/or

• Serum Aspartate Aminotransferase (AST) > triple the upper limit of the normal value range and/or

• Severe renal dysfunction, defined as:

• Serum creatinine > twice the upper limit of the normal range

• Chronic Kidney Disease (glomerular filtration rate <45 Milliliter per minute).

• Hyperthyroidism or hypothyroidism.

• Severe infectious disease, example (eg) Human Immunodeficiency Virus positive or active tuberculosis.

• Severe autoimmune disease, e.g. lupus erythematosus, multiple sclerosis.

• Severe respiratory, digestive, hematological disease (including Anemia of Hb < 100 gram per litre) or tumor.

• Known to be hypersensitivity to Bisoprolol, or any of the excipient.

• Substance or alcohol abuse.

• Received heart transplantation or pacemaker implantation; revascularization treatment within 3 months; or plan to receive above treatment in 6 months.

• Currently undertaking other treatment that may affect the safety and/or efficacy evaluation, e.g. beta receptors agonists, et cetera.

• No legal ability or legal ability is limited.

• Subjects unlikely to cooperate in the study or with inability or unwillingness to give informed consent.

• Child-bearing period women without effective contraceptive measures, pregnancy and lactation.

• Participation in another clinical trial within the past 90 days.

• Other significant condition that in the Investigator's opinion would exclude the subject from the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fuwai Hospital Chinese Academy of Medical Sciences	Beijing		China	100037

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany
• Merck Serono Co., Ltd., China

Investigators

• Study Director: Medical Responsible, Merck Serono Co., Ltd., China

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2016

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT03026088
• Other Study ID Numbers: MS200006-0039
• First Posted: Jan 20, 2017
• Last Update Posted: Jan 29, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck KGaA, Darmstadt, Germany: Chronic Heart Failure; Bisoprolol; Heart rate control
• Additional relevant MeSH terms: Heart Failure; Bisoprolol

Study Results

Participant Flow

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Period Title: Overall Study
STARTED	20
COMPLETED	0
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Overall Participants	20
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.37 (13.931)
Sex: Female, Male (Count of Participants)
Female	5 25%
Male	15 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Resting Heart Rate at Week 6
Description	Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

2. Secondary Outcome

Title	Change From Baseline in Resting Heart Rate at Week 3, 10 and 18
Description	Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Time Frame	Baseline, Week 3, 10 and 18

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

3. Secondary Outcome

Title	Left Ventricular Ejection Fraction (LVEF) at Baseline, Week 14 and 26
Description	LVEF was defined as the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat and it is used to measure the cardiac output for the heart. Ultrasound cardiogram performed to measure LVEF.
Time Frame	Baseline, Week 14 and 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

4. Secondary Outcome

Title	Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26
Description	Left Ventricular End-Systolic Dimension was measured by Ultrasound cardiogram.
Time Frame	Baseline, Week 14 and 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

5. Secondary Outcome

Title	Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26
Description	Left Ventricular End-diastolic Dimension was measured by Ultrasound cardiogram.
Time Frame	Baseline, Week 14 and 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

6. Secondary Outcome

Title	Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26
Description	Interventricular septal thickness was measured by Ultrasound cardiogram.
Time Frame	Baseline, Week 14 and 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

7. Secondary Outcome

Title	Ratio of Early (E) to Late (A) Ventricular Filling Velocities (E/A Ratio) at Baseline, Week 14 and Week 26
Description	Early to late ratio was measured by ultrasound cardiogram.
Time Frame	Baseline, Week 14 and Week 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

8. Secondary Outcome

Title	Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure
Description	Blood pressure (systolic and diastolic) measurement was taken at sitting position, with the elbow at the same level with the heart. Number of participants with clinically relevant systolic and diastolic blood pressure reported based on the assessment of the investigator.
Time Frame	Screening (Week -2) up to Week 26

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Count of Participants [Participants]	0 0%

9. Secondary Outcome

Title	Number of Participants With New York Heart Association (NYHA) Class
Description	The NYHA classification assesses the severity of symptoms of heart failure. Here NYHA class of II - IV was assessed. NYHA II: Slight limitation of physical activity, comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue or palpitation. NYHA III: Marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes undue breathlessness, fatigue or palpitation. NYHA IV: Unable to carry on any physical activity without discomfort, symptoms at rest can be present. If any physical activity is undertaken, discomfort increased.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Baseline: NYHA class II	10 50%
Baseline: NYHA class III	10 50%
Baseline: NYHA class IV	0 0%
Week 26: NYHA class II	2 10%
Week 26: NYHA class III	1 5%
Week 26: NYHA class IV	0 0%
Week 26: Not evaluated	17 85%

10. Secondary Outcome

Title	Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm
Description	Resting heart rate measurement was taken at sitting position for a continuous record of 3 minutes. Heartbeats in each minute was calculated and averaged to obtain the resting heart rate.
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received at least one dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Number [percentage of participants]	0 0%

11. Secondary Outcome

Title	Quality of Life Based on Minnesota Living With Heart Failure (MLHF) at Baseline and End of Treatment
Description	MLHF questionnaire has 21 items. Questions assess the impact of frequent physical symptoms of heart failure and the effects of heart failure on physical and social functions. Each question had a possible score of 0 (best) to 5 (worst), for a total of 0 to 105. The higher the summed score, the worse is the impact of heart failure on a participant's quality of life.
Time Frame	Baseline, end of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

12. Secondary Outcome

Title	Quality of Life Based on the Medical Outcomes Study Item Short From Health Survey (SF-36) at Baseline and End of Treatment
Description	Short Form Health Survey (SF-36), an instrument composed by 8 subscales: Physical Functioning, Physical Role Function, Bodily Pain, General Health, Vitality, Social Functioning, Emotional Role Function and Mental Health. The individual question items (Likert scale 0-4) are first summed for each item under the various sections. Then, those summary scores are then standardized on a scale between 0 and 1 using the mean and standard deviation of the actual scores and finally, weighted to a scale between 0 and 100. The items contributing to a scale are scored so that a higher score represents better health, and they are averaged together to create the scale score. Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
Time Frame	Baseline, end of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

13. Secondary Outcome

Title	6-Minute Walk Test
Description	6-min walk test was a practical simple test that requires a 100-feet hallway but no exercise equipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired participants. This test measures the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.
Time Frame	Baseline and End of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

14. Secondary Outcome

Title	Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP)
Description	Routine blood tests was performed to measure NT Pro-BNP. The normal range for NT Pro-BNP varies from 0 picograms/milliliter (pg/mL) (lower limit of normal value) -125 pg/mL (upper limit of normal value).
Time Frame	Baseline up to End of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Count of Participants [Participants]	19 95%

15. Secondary Outcome

Title	Mean 24 Hour, Day Time and Night Time Heart Rate
Description	Holter monitor was used to measure heart rate (24 hour, day time, night time).
Time Frame	Baseline, week 6, 14 and end of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

16. Secondary Outcome

Title	Number of Participants With Arrhythmia
Description	Holter monitor was used to diagnose arrhythmia.
Time Frame	Baseline up to end of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Count of Participants [Participants]	0 0%

17. Secondary Outcome

Title	Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm
Description	Holter monitor was used to measure heart rate.
Time Frame	Baseline, week 6, 14 and end of treatment (Week 26)

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
Count of Participants [Participants]	0 0%

18. Secondary Outcome

Title	Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
Description	MPR is used to assess the medicine compliance. MPR is defined as the actual drug number taken by the participants divided by the drug number should be taken by the participants according to the protocol. MPR between 80%-100% is defined as good compliance. Medication rate of less than (<) 80% or greater than (>)100% is defined as insufficient compliance.
Time Frame	Up to Week 26

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
MPR: Good Compliance	18 90%
MPR: Insufficient compliance	0 0%
Not evaluated	2 10%

19. Secondary Outcome

Title	Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
Description	Number of participants with all-cause mortality, cardiac death, or re-admission due to heart failure was reported.
Time Frame	Up to Week 26

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose of study treatment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	20
All-cause mortality	1 5%
Cardiac death	0 0%
Re-admission due to heart failure	0 0%

20. Primary Outcome

Title	Change From Baseline in Resting Heart Rate at Week 14
Description	Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Time Frame	Baseline, Week 14

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

21. Primary Outcome

Title	Change From Baseline in Resting Heart Rate at Week 26
Description	Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Data was not collected since the study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants which led barrier to the recruitment.

Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
Measure Participants	0

Adverse Events

Time Frame	Baseline up to Week 26
Arm/Group Title	Bisoprolol
Arm/Group Description	Participants received Bisoprolol orally, once daily at a dose of 1.25 milligram (mg) up to Weeks 3, and then it was up-titrated to 2.5 mg up to Week 6, 3.75 mg up to Week 10, 5 mg up to Week 14, 7.5 mg up to Week 18 and 10 mg up to Week 26.
All Cause Mortality
	Bisoprolol
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Serious Adverse Events
	Bisoprolol
	Affected / at Risk (%)	# Events
Total	4/20 (20%)
Cardiac disorders
Cardiac failure acute	1/20 (5%)
General disorders
Sudden death	1/20 (5%)
Nervous system disorders
Cerebral infarction	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea at rest	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Bisoprolol
	Affected / at Risk (%)	# Events
Total	10/20 (50%)
Cardiac disorders
Angina pectoris	1/20 (5%)
Sinoatrial block	1/20 (5%)
Sinus bradycardia	1/20 (5%)
Gastrointestinal disorders
Diarrhoea	1/20 (5%)
Infections and infestations
Nasopharyngitis	1/20 (5%)
Upper respiratory tract infection 3 (15.0)	3/20 (15%)
Investigations
Blood uric acid increased	1/20 (5%)
Weight increased	1/20 (5%)
Metabolism and nutrition disorders
Diabetes mellitus	1/20 (5%)
Hyperglycemia	1/20 (5%)
Skin and subcutaneous tissue disorders
Rash	1/20 (5%)
Vascular disorders
Hypertension	1/20 (5%)
Hypotension	1/20 (5%)

Limitations/Caveats

The study was terminated early due to limited beta-blocker naive participants among newly diagnosed heart failure participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.