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| Name | Class |
|---|---|
| Merck Ltd. | INDUSTRY |
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This is a prospective, open-labeled, multi-centric trial to evaluate the effect of bisoprolol (between low dose and high dose) on surrogate markers of heart failure in Korea.
Subjects with systolic congestive heart failure (CHF) will be enrolled in this study after proper evaluation of NT-proBNP, global assessment of CHF, 6-minute walking test and improvement score of New York Heart Association (NYHA) and echocardiogram (left ventricular chamber size and ejection fraction [LVEF]). Each subject will be orally administered bisoprolol for 6 months starting at 1.25 mg at the Week 0 and titrated up to 10 mg during the 6 month period if the persistent standing systolic blood pressure (SBP) is greater than (>) 90 millimeter of mercury (mm Hg) and there is no symptom of hypotension at the current dose medication (syncope, loss of consciousness, dizziness when standing up).
OBJECTIVES
Primary objective:
• To evaluate the effect of bisoprolol (between low dose and high dose) on surrogate markers of heart failure in Korea
Secondary objectives:
To evaluate bisoprolol for the effects on clinical improvement of heart failure in Korea:
Hospitalization due to heart failure
To evaluate the safety and tolerability of bisoprolol
Global assessment of CHF
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose Bisoprolol | Experimental |
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| High Dose Bisoprolol | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Dose Bisoprolol | Drug | Bisoprolol tablet (Concor) will be administered orally at a starting dose of 1.25 milligram (mg) once daily for 2 weeks. The dose will be further escalated from 1.25 mg to 2.5 mg once daily after 2 weeks and will be administered up to 26 weeks, only if the previous administered dose is well tolerated. If the subject could not tolerate the increased dose, then the last tolerated dose will be maintained up to 26 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26 | B-type natriuretic peptide (BNP) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function. The percent change of NT-pro BNP was calculated according to the formula: N-terminal pro B-type natriuretic peptide (NT-proBNP) reduction ratio = 100*(Baseline NT-proBNP - Week 26 NT-proBNP)/Baseline NT-proBNP. | Baseline and Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Classified as Class I to IV According to New York Heart Association (NYHA) | New York Heart Association (NYHA) classification of heart failure: Class I: No limitation: ordinary physical exercise does not cause undue fatigue, dyspnea, or palpitations. Class II: Slight limitation of physical activity: comfortable at rest but ordinary activity results in fatigue, palpitations, or dyspnea. Class III: Marked limitation of physical activity: comfortable at rest but less than ordinary activity results in symptoms. Class IV: Unable to carry out any physical activity without discomfort: symptoms of heart failure are present even at rest with increased discomfort with any physical activity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Konkuk University Medical Center | Seoul | South Korea |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 1.25 milligram (mg) once daily for 2 weeks. The dose was further escalated from 1.25 mg to 2.5 mg once daily after 2 weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| High Dose Bisoprolol | Drug | Bisoprolol tablet (Concor) will be administered orally at a starting dose of 3.75 mg once daily for 2 weeks. The dose will be subsequently increased to 5 mg, 7.5 mg, or 10 mg once daily every two weeks and will be administered up to 26 weeks, only if the previous administered dose is well tolerated. If the subject could not tolerate the increased dose, then the last tolerated dose will be maintained up to 26 weeks. |
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| Baseline and Week 26 |
| Change From Baseline in 6-minute Walking Test (6-MWT) Distance at Week 26 | 6-minute Walking Test (6-MWT) distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. | Baseline and Week 26 |
| Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Week 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. | Baseline and Week 26 |
| Change From Baseline in Echocardiographic Left Ventricular Size at Week 26 | Left ventricle size was measured as systolic and diastolic Left Ventricular Internal Dimension (LVID). Diastolic dimension was measured of the left ventricle at the level of the chordae tendineae. The systolic dimension was measured as the smallest dimension between the left septal endocardium and the posterior wall endocardium during systole, whether or not the two walls were exactly apposed. | Baseline and Week 26 |
| Number of Participants Who Were Re-hospitalized Due to Heart Failure and Who Died Due to Cardiovascular Disorder | Baseline up to Week 26 |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. | Baseline up to Week 26 |
| Mean Change From Baseline in Global Assessment of Congestive Heart Failure (CHF) Score at Week 26 | Global assessment of CHF: The Investigator defined, graded, and recorded the participant's symptoms and signs by using a 6-point CHF scale ranging from 0 (unassessable), 1 (worsened), 2 (no change), 3 (mildly improved), 4 (moderately improved) and 5 (markedly improved). | Baseline and Week 26 |
| FG001 | High Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 3.75 mg once daily for 2 weeks. The dose was subsequently increased to 5 mg, 7.5 mg, or 10 mg once daily every two weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. |
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Intention-to-treat (ITT) population included all the randomized participants who had at least one dose of the investigational product. Baseline data has been provided for 159 participants (ITT population).
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 1.25 milligram (mg) once daily for 2 weeks. The dose was further escalated from 1.25 mg to 2.5 mg once daily after 2 weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. |
| BG001 | High Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 3.75 mg once daily for 2 weeks. The dose was subsequently increased to 5 mg, 7.5 mg, or 10 mg once daily every two weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26 | B-type natriuretic peptide (BNP) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function. The percent change of NT-pro BNP was calculated according to the formula: N-terminal pro B-type natriuretic peptide (NT-proBNP) reduction ratio = 100*(Baseline NT-proBNP - Week 26 NT-proBNP)/Baseline NT-proBNP. | ITT population included all the randomized participants who had at least one dose of the investigational product. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. | Posted | Mean | Standard Deviation | Percent change | Baseline and Week 26 |
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| Secondary | Percentage of Participants Classified as Class I to IV According to New York Heart Association (NYHA) | New York Heart Association (NYHA) classification of heart failure: Class I: No limitation: ordinary physical exercise does not cause undue fatigue, dyspnea, or palpitations. Class II: Slight limitation of physical activity: comfortable at rest but ordinary activity results in fatigue, palpitations, or dyspnea. Class III: Marked limitation of physical activity: comfortable at rest but less than ordinary activity results in symptoms. Class IV: Unable to carry out any physical activity without discomfort: symptoms of heart failure are present even at rest with increased discomfort with any physical activity. | ITT population included all the randomized participants who had at least one dose of the investigational product. | Posted | Number | Percentage of participants | Baseline and Week 26 |
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| Secondary | Change From Baseline in 6-minute Walking Test (6-MWT) Distance at Week 26 | 6-minute Walking Test (6-MWT) distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. | ITT population included all the randomized participants who had at least one dose of the investigational product. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Mean | Standard Deviation | Meter | Baseline and Week 26 |
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| Secondary | Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Week 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. | ITT population included all the randomized participants who had at least one dose of the investigational product. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Mean | Standard Deviation | Percent LVEF | Baseline and Week 26 |
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| Secondary | Change From Baseline in Echocardiographic Left Ventricular Size at Week 26 | Left ventricle size was measured as systolic and diastolic Left Ventricular Internal Dimension (LVID). Diastolic dimension was measured of the left ventricle at the level of the chordae tendineae. The systolic dimension was measured as the smallest dimension between the left septal endocardium and the posterior wall endocardium during systole, whether or not the two walls were exactly apposed. | ITT population included all the randomized participants who had at least one dose of the investigational product. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Mean | Standard Deviation | Milliliter LVID | Baseline and Week 26 |
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| Secondary | Number of Participants Who Were Re-hospitalized Due to Heart Failure and Who Died Due to Cardiovascular Disorder | ITT population included all the randomized participants who had at least one dose of the investigational product. | Posted | Number | Participants | Baseline up to Week 26 |
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| Secondary | Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. | Safety analysis population included all the randomized participants who had at least one dose of the investigational product had post-dose safety data confirmed at least once by the Investigator. | Posted | Number | Participants | Baseline up to Week 26 |
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| Secondary | Mean Change From Baseline in Global Assessment of Congestive Heart Failure (CHF) Score at Week 26 | Global assessment of CHF: The Investigator defined, graded, and recorded the participant's symptoms and signs by using a 6-point CHF scale ranging from 0 (unassessable), 1 (worsened), 2 (no change), 3 (mildly improved), 4 (moderately improved) and 5 (markedly improved). | ITT population included all the randomized participants who had at least one dose of the investigational product. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 26 |
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Baseline up to Week 26
An AE is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 1.25 milligram (mg) once daily for 2 weeks. The dose was further escalated from 1.25 mg to 2.5 mg once daily after 2 weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. | 16 | 66 | 45 | 66 | ||
| EG001 | High Dose Bisoprolol | Bisoprolol tablet (Concor) administered orally at a starting dose of 3.75 mg once daily for 2 weeks. The dose was subsequently increased to 5 mg, 7.5 mg, or 10 mg once daily every two weeks and was administered up to 26 weeks, only if the previous administered dose was well tolerated. If the participant didn't tolerate the increased dose, then the last tolerated dose was maintained up to 26 weeks. | 9 | 114 | 71 | 114 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Chest Pain | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Sudden cardiac death | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Diabetic foot | Metabolism and nutrition disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Insomnia | Nervous system disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Flank pain | Renal and urinary disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Nasopharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Asthenia | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Oedema | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (15.0) | Non-systematic Assessment |
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The investigator commits him/her to forward to sponsor all papers, manuscripts or conference abstracts intended for publication or presentation that contain data or results generated in connection with the study. Papers and abstracts must be available at sponsor's site in time before the planned submission date to allow for review and comments. Submission for publication need expressed written permission from the sponsor. Any publication should follow publication policy as described in protocol.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D054143 | Heart Failure, Systolic |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017298 | Bisoprolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
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