search
Back to results

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

Primary Purpose

Heart Failure

Status
Terminated
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Bisoprolol
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Chronic Heart Failure, Bisoprolol, Heart rate control

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Fuwai Hospital Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bisoprolol

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Resting Heart Rate at Week 6
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Change From Baseline in Resting Heart Rate at Week 14
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Change From Baseline in Resting Heart Rate at Week 26
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.

Secondary Outcome Measures

Change From Baseline in Resting Heart Rate at Week 3, 10 and 18
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Left Ventricular Ejection Fraction (LVEF) at 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.
Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26
Left Ventricular End-Systolic Dimension was measured by Ultrasound cardiogram.
Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26
Left Ventricular End-diastolic Dimension was measured by Ultrasound cardiogram.
Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26
Interventricular septal thickness was measured by Ultrasound cardiogram.
Ratio of Early (E) to Late (A) Ventricular Filling Velocities (E/A Ratio) at Baseline, Week 14 and Week 26
Early to late ratio was measured by ultrasound cardiogram.
Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure
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.
Number of Participants With New York Heart Association (NYHA) Class
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.
Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm
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.
Quality of Life Based on Minnesota Living With Heart Failure (MLHF) at Baseline and End of Treatment
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.
Quality of Life Based on the Medical Outcomes Study Item Short From Health Survey (SF-36) at Baseline and End of Treatment
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.
6-Minute Walk Test
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.
Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP)
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).
Mean 24 Hour, Day Time and Night Time Heart Rate
Holter monitor was used to measure heart rate (24 hour, day time, night time).
Number of Participants With Arrhythmia
Holter monitor was used to diagnose arrhythmia.
Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm
Holter monitor was used to measure heart rate.
Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
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.
Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
Number of participants with all-cause mortality, cardiac death, or re-admission due to heart failure was reported.

Full Information

First Posted
January 12, 2017
Last Updated
January 20, 2020
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Serono Co., Ltd., China
search

1. Study Identification

Unique Protocol Identification Number
NCT03026088
Brief Title
Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants
Acronym
Biso-CHF
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Limited beta-blocker naive participants among newly diagnosed heart failure participants, which led barrier to the recruitments.
Study Start Date
March 21, 2017 (Actual)
Primary Completion Date
December 26, 2018 (Actual)
Study Completion Date
December 26, 2018 (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

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Chronic Heart Failure, Bisoprolol, Heart rate control

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bisoprolol
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bisoprolol
Other Intervention Name(s)
Brand name: Concor
Intervention 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.
Primary Outcome Measure Information:
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
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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)
Title
Number of Participants With Arrhythmia
Description
Holter monitor was used to diagnose arrhythmia.
Time Frame
Baseline up to end of treatment (Week 26)
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)
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Serono Co., Ltd., China
Official's Role
Study Director
Facility Information:
Facility Name
Fuwai Hospital Chinese Academy of Medical Sciences
City
Beijing
ZIP/Postal Code
100037
Country
China

12. IPD Sharing Statement

Learn more about this trial

Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants

We'll reach out to this number within 24 hrs