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A Prospective, Open-labeled, Multi-centric Trial in Subjects With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea (PRISM)

Primary Purpose

Heart Failure, Congestive

Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Low Dose Bisoprolol
High Dose 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, Congestive focused on measuring Systolic heart failure, Bisoprolol, Concor, Echocardiogram

Eligibility Criteria

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

Inclusion Criteria:

  • Subjects with heart failure and at the age of 18 (inclusive) to 80 (exclusive)
  • Subjects with NYHA Class II-IV with dyspnea
  • Subjects with left ventricular ejection fraction (LVEF) of 40 percent or below on the echocardiogram
  • Eligible subjects who meet the criteria, are capable of participating in the study, and provide written informed consent to study participation after receiving a clear explanation about the study objective and nature

Exclusion Criteria:

  • A subject who cannot understand or does not agree to the study contents
  • Subjects with conduction defect of 2nd degree or above atrioventricular block
  • Subjects with heart rate less than (<) 60 beats at rest
  • Subjects with systolic blood pressure < 100 mm Hg at rest
  • Subjects with renal failure (serum creatinine > 2.0 milligram per deciliter [mg/dL])
  • Subjects with unrecovered pulmonary edema
  • Subjects with history of myocardial infarction or stroke within 3 months
  • Subjects with history of coronary intervention or coronary bypass within 6 months
  • Subjects with heart failure due to mitral valve without valve replacement or aortic valvular disease (excluding moderate or less severe mitral insufficiency secondary to left ventricular expansion)
  • Subjects with history of valve replacement within the past 6 months
  • Subjects with history or scheduled heart transplantation
  • Subjects with reversible obstructive pulmonary disease
  • Subjects with other cases where beta blockers are contraindicated
  • Any surgical or internal disease that may put the subject at a higher risk due to study participation or may interfere with the subjects compliance to study requirements or completion of the study, based on the judgment of the Investigator
  • A subject with history of non-compliance to drug prescriptions or who is not willing to comply with the protocol
  • Subjects with a history of treated or untreated malignant tumor within the past 5 years
  • Pregnant or lactating women
  • Subjects with heart failure due to acute myocarditis
  • Subjects with continuous ventricular tachycardia with history of syncope within 3 months

Sites / Locations

  • Konkuk University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Low Dose Bisoprolol

High Dose Bisoprolol

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Number of Participants Who Were Re-hospitalized Due to Heart Failure and Who Died Due to Cardiovascular Disorder
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.
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).

Full Information

First Posted
February 22, 2010
Last Updated
January 13, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT01074307
Brief Title
A Prospective, Open-labeled, Multi-centric Trial in Subjects With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea
Acronym
PRISM
Official Title
Prospective, Open-labeled Trial in Patients With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea (PRISM)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
Collaborators
Merck Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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: New York Heart Association (NYHA), 6-minutes walking test Echocardiogram (left ventricular chamber size and LVEF) Hospitalization due to heart failure To evaluate the safety and tolerability of bisoprolol Global assessment of CHF

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Congestive
Keywords
Systolic heart failure, Bisoprolol, Concor, Echocardiogram

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Dose Bisoprolol
Arm Type
Experimental
Arm Title
High Dose Bisoprolol
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Low Dose Bisoprolol
Other Intervention Name(s)
Concor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
High Dose Bisoprolol
Other Intervention Name(s)
Concor
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26
Description
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.
Time Frame
Baseline and Week 26
Secondary Outcome Measure Information:
Title
Percentage of Participants Classified as Class I to IV According to New York Heart Association (NYHA)
Description
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.
Time Frame
Baseline and Week 26
Title
Change From Baseline in 6-minute Walking Test (6-MWT) Distance at Week 26
Description
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.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Week 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.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Echocardiographic Left Ventricular Size at Week 26
Description
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.
Time Frame
Baseline and Week 26
Title
Number of Participants Who Were Re-hospitalized Due to Heart Failure and Who Died Due to Cardiovascular Disorder
Time Frame
Baseline up to Week 26
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Baseline up to Week 26
Title
Mean Change From Baseline in Global Assessment of Congestive Heart Failure (CHF) Score at Week 26
Description
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).
Time Frame
Baseline and 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: Subjects with heart failure and at the age of 18 (inclusive) to 80 (exclusive) Subjects with NYHA Class II-IV with dyspnea Subjects with left ventricular ejection fraction (LVEF) of 40 percent or below on the echocardiogram Eligible subjects who meet the criteria, are capable of participating in the study, and provide written informed consent to study participation after receiving a clear explanation about the study objective and nature Exclusion Criteria: A subject who cannot understand or does not agree to the study contents Subjects with conduction defect of 2nd degree or above atrioventricular block Subjects with heart rate less than (<) 60 beats at rest Subjects with systolic blood pressure < 100 mm Hg at rest Subjects with renal failure (serum creatinine > 2.0 milligram per deciliter [mg/dL]) Subjects with unrecovered pulmonary edema Subjects with history of myocardial infarction or stroke within 3 months Subjects with history of coronary intervention or coronary bypass within 6 months Subjects with heart failure due to mitral valve without valve replacement or aortic valvular disease (excluding moderate or less severe mitral insufficiency secondary to left ventricular expansion) Subjects with history of valve replacement within the past 6 months Subjects with history or scheduled heart transplantation Subjects with reversible obstructive pulmonary disease Subjects with other cases where beta blockers are contraindicated Any surgical or internal disease that may put the subject at a higher risk due to study participation or may interfere with the subjects compliance to study requirements or completion of the study, based on the judgment of the Investigator A subject with history of non-compliance to drug prescriptions or who is not willing to comply with the protocol Subjects with a history of treated or untreated malignant tumor within the past 5 years Pregnant or lactating women Subjects with heart failure due to acute myocarditis Subjects with continuous ventricular tachycardia with history of syncope within 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Konkuk University Medical Center
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

A Prospective, Open-labeled, Multi-centric Trial in Subjects With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea

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