Heart FailurePhase 4Biso-CHFNCT03026088
Efficacy of Oral Bisoprolol on Heart Rate Reduction in Chinese Chronic Heart Failure Participants
A Phase 4 study testing Bisoprolol in people with Heart Failure, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
Trial summary
This is a single-arm, open label, interventional, multi-center, phase 4 pilot study. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Bisoprolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 21 Mar 2017to 26 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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].
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
This is a single-arm, open label, interventional, multi-center, phase 4 pilot study.
- Conditions
- Heart Failure
- Being tested
- Bisoprolol
- Keywords
- Chronic Heart Failure, Bisoprolol, Heart rate control
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BisoprololDrug
Also called Brand name: Concor
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.
| Study group | Role | What they receive |
|---|---|---|
| Bisoprolol | Experimental | Not described Receives: Drug: Bisoprolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Resting Heart Rate at Week 6
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Measured: Baseline, Week 6
Change From Baseline in Resting Heart Rate at Week 14
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Measured: Baseline, Week 14
Change From Baseline in Resting Heart Rate at Week 26
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
Measured: Baseline, Week 26
Secondary outcomes (18)
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.
Measured: Baseline, Week 3, 10 and 18
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.
Measured: Baseline, Week 14 and 26
Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26
Left Ventricular End-Systolic Dimension was measured by Ultrasound cardiogram.
Measured: Baseline, Week 14 and 26
Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26
Left Ventricular End-diastolic Dimension was measured by Ultrasound cardiogram.
Measured: Baseline, Week 14 and 26
Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26
Interventricular septal thickness was measured by Ultrasound cardiogram.
Measured: Baseline, Week 14 and 26
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.
Measured: Baseline, Week 14 and Week 26
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.
Measured: Screening (Week -2) up to Week 26
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.
Measured: Baseline, Week 26
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.
Measured: Baseline up to Week 26
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.
Measured: Baseline, end of treatment (Week 26)
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.
Measured: Baseline, end of treatment (Week 26)
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.
Measured: Baseline and End of treatment (Week 26)
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).
Measured: Baseline up to End of treatment (Week 26)
Mean 24 Hour, Day Time and Night Time Heart Rate
Holter monitor was used to measure heart rate (24 hour, day time, night time).
Measured: Baseline, week 6, 14 and end of treatment (Week 26)
Number of Participants With Arrhythmia
Holter monitor was used to diagnose arrhythmia.
Measured: Baseline up to end of treatment (Week 26)
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.
Measured: Baseline, week 6, 14 and end of treatment (Week 26)
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.
Measured: Up to Week 26
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.
Measured: Up to Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2017 (estimated)
- Study start21 Mar 2017
- Primary completion26 Dec 2018
- Study completion26 Dec 2018
Why it stopped: Limited beta-blocker naive participants among newly diagnosed heart failure participants, which led barrier to the recruitments.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Serono Co., Ltd., China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03026088
- Sponsor's protocol ID
- MS200006-0039
- Acronym
- Biso-CHF
- Status last verified
- Jan 2020
- First submitted
- 12 Jan 2017
- Last updated
- 29 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03026088
- Acronym / sponsor ID
- Biso-CHF / MS200006-0039
- Conditions
- Heart Failure
- Keywords
- Chronic Heart Failure, Bisoprolol, Heart rate control
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Limited beta-blocker naive participants among newly diagnosed heart failure participants, which led barrier to the recruitments.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono Co., Ltd., China
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 26 Dec 2018 (actual)
- Study completion
- 26 Dec 2018 (actual)
- First posted
- 20 Jan 2017 (estimated)
- Results
- Posted 29 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, open label, interventional, multi-center, phase 4 pilot study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bisoprolol | Experimental | Drug: Bisoprolol |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (42 listed)
- 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].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BisoprololAlso: Brand name: ConcorParticipants 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. | Drug | Bisoprolol |
Primary outcome
Change From Baseline in Resting Heart Rate at Week 6
Time frame: Baseline, 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
Time frame: Baseline, 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
Time frame: Baseline, Week 26
Heartbeats in each minute were calculated and averaged to obtain the resting heart rate.
18 secondary outcomes
Change From Baseline in Resting Heart Rate at Week 3, 10 and 18
Time frame: Baseline, Week 3, 10 and 18
Left Ventricular Ejection Fraction (LVEF) at Baseline, Week 14 and 26
Time frame: Baseline, Week 14 and 26
Left Ventricular End-Systolic Dimension (LVESD) at Baseline, Week 14 and 26
Time frame: Baseline, Week 14 and 26
Left Ventricular End-diastolic Dimension (LVEDD) at Baseline, Week 14 and 26
Time frame: Baseline, Week 14 and 26
Interventricular Septal Thickness (IVST) at Baseline, Week 14 and 26
Time frame: Baseline, Week 14 and 26
Ratio of Early (E) to Late (A) Ventricular Filling Velocities (E/A Ratio) at Baseline, Week 14 and Week 26
Time frame: Baseline, Week 14 and Week 26
Number of Participants With Clinically Relevant Systolic and Diastolic Blood Pressure
Time frame: Screening (Week -2) up to Week 26
Number of Participants With New York Heart Association (NYHA) Class
Time frame: Baseline, Week 26
Percentage of Participants With Resting Heart Rate Less Than 70 Beats Per Minute (Bpm) and More Than 55 Bpm
Time frame: Baseline up to Week 26
Quality of Life Based on Minnesota Living With Heart Failure (MLHF) at Baseline and End of Treatment
Time frame: Baseline, end of treatment (Week 26)
Quality of Life Based on the Medical Outcomes Study Item Short From Health Survey (SF-36) at Baseline and End of Treatment
Time frame: Baseline, end of treatment (Week 26)
6-Minute Walk Test
Time frame: Baseline and End of treatment (Week 26)
Number of Participants With Abnormal Value of N-terminal Pro-B-type Natriuretic Peptide (NT Pro-BNP)
Time frame: Baseline up to End of treatment (Week 26)
Mean 24 Hour, Day Time and Night Time Heart Rate
Time frame: Baseline, week 6, 14 and end of treatment (Week 26)
Number of Participants With Arrhythmia
Time frame: Baseline up to end of treatment (Week 26)
Number of Participants With 24 Hour Heart Rate With More Than 70 Beats Per Minute (Bpm) and Less Than 55 Bpm
Time frame: Baseline, week 6, 14 and end of treatment (Week 26)
Number of Participants With Medicine Compliance Assessed by Medication Procession Ratio (MPR)
Time frame: Up to Week 26
Number of Participants With All Cause Mortality, Cardiac Death, or Re-admission Due to Heart Failure
Time frame: Up to Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Serono Co., Ltd., China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bisoprolol in people with Heart Failure, run by Merck KGaA, Darmstadt, Germany at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Resting Heart Rate at Week 6 (time frame: Baseline, Week 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2020.