Clinical trial NCT03026088: Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants
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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Chronic Heart Failure
Bisoprolol
Heart rate control
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Serono Co., Ltd., China
First posted: 2017-01-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change From Baseline in Resting Heart Rate at Week 6
timeFrame: Baseline, Week 6
measure: Change From Baseline in Resting Heart Rate at Week 14
timeFrame: Baseline, Week 14
measure: Change From Baseline in Resting Heart Rate at Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline in Resting Heart Rate at Week 3, 10 and 18
timeFrame: Baseline, Week 3, 10 and 18
measure: Left Ventricular Ejection Fraction (LVEF) at Baseline, Week 14 and 26
timeFrame: Baseline, Week 14 and 26
measure: Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26
timeFrame: Baseline, Week 14 and 26
measure: Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26
timeFrame: Baseline, Week 14 and 26
measure: Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26
timeFrame: Baseline, Week 14 and 26
measure: Ratio of Early (E) to Late (A) Ventricular Filling Velocities (E/A Ratio) at Baseline, Week 14 and Week 26
timeFrame: Baseline, Week 14 and Week 26
measure: Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure
timeFrame: Screening (Week -2) up to Week 26
measure: Number of Participants With New York Heart Association (NYHA) Class
timeFrame: Baseline, Week 26
measure: Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm
timeFrame: Baseline up to Week 26
measure: Quality of Life Based on Minnesota Living With Heart Failure (MLHF) at Baseline and End of Treatment
timeFrame: Baseline, end of treatment (Week 26)
measure: Quality of Life Based on the Medical Outcomes Study Item Short From Health Survey (SF-36) at Baseline and End of Treatment
timeFrame: Baseline, end of treatment (Week 26)
measure: 6-Minute Walk Test
timeFrame: Baseline and End of treatment (Week 26)
measure: Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP)
timeFrame: Baseline up to End of treatment (Week 26)
measure: Mean 24 Hour, Day Time and Night Time Heart Rate
timeFrame: Baseline, week 6, 14 and end of treatment (Week 26)
measure: Number of Participants With Arrhythmia
timeFrame: Baseline up to end of treatment (Week 26)
measure: Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm
timeFrame: Baseline, week 6, 14 and end of treatment (Week 26)
measure: Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
timeFrame: Up to Week 26
measure: Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
timeFrame: Up to Week 26
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital Chinese Academy of Medical Sciences
Study officials:
affiliation: Merck Serono Co., Ltd., China
name: Medical Responsible
role: STUDY_DIRECTOR
References: