The Cardiac Insufficiency BIsoprolol Study in Japanese Patients With Chronic Heart Failure (CIBIS-J)
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 220
- Locations
- 110
- Primary Endpoint
- Tolerability: The probability that administered maintenance dose reaches the maximum (bisoprolol 5 mg/day, carvedilol 20 mg/day)
Study Overview
Brief Summary
The purpose of this study is to investigate the non-inferiority of bisoprolol to carvedilol by evaluating tolerability (The probability that administered maintenance dose reaches the maximum will be determined as an indicator) as a primary endpoint when bisoprolol or carvedilol is administered for 48 weeks to Japanese chronic heart failure patients. In addition, the safety and efficacy of bisoprolol will be investigated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •As a result of diagnosis and tests before registration, a patient who is considered by an investigator to meet all requirements and to have ability to consent can be enrolled.
- •Primary disease: In principle, ischemic heart disease or dilated cardiomyopathy.
- •Heart failure patients with 40% or less of left ventricular ejection fraction (LVEF) .
- •Patients in NYHA functional classification Class II, III, or IV (including a medical history).
- •Basic treatment: In principle, patients undergoing treatment with an ACE inhibitor (or angiotensin receptor blocker (ARB)), a diuretic, a digitalis preparation, etc.
- •Patients who had not undergone treatment with a beta-blocker (except eye drops) within 8 weeks before the registration date.
- •Age: Patients aged 20 to less than 85 on the day of obtaining written informed consent.
- •Hospitalized/outpatient: Either hospitalized or outpatient status.
- •Gender: Male or Female
Exclusion Criteria
- •Patients who meet any of the following exclusion criteria at the time of registration will be excluded:
- •Patients who are considered not to be candidates for administration of bisoprolol or carvedilol.
- •Patients who have developed acute myocardial infarction within 8 weeks before the registration day.
- •Patients who have history of stroke or serious cerebrovascular accident within 1 year before the registration day.
- •Patients with poor prognosis and life-threatening disease, such as malignant tumor, or such medical history within 5 years before the registration day.
- •Patients who are scheduled to undergo coronary revascularization (Coronary artery bypass grafting; CABG, Percutaneous coronary intervention; PCI) during the study period.
- •Patients who are pregnant, lactating, may become pregnant, or want to become pregnant during the study.
- •Patients from whom written informed consent cannot be obtained.
- •Patients who are judged by an investigator to be inappropriate for this study for any other reason.
Arms & Interventions
Bisoprolol group
Daily oral administration of bisoprolol 0.625 mg tablet once a day should be given (Step 1). If tolerability is confirmed by an investigator, the dose should be increased to 1.25 mg (bisoprolol 0.625 mg, 2 tablets; or bisoprolol 2.5 mg, half tablet; once daily) (Step 2). In the same manner, the doses should be increased to 2.5 mg (bisoprolol 2.5 mg, 1 tablet; or bisoprolol 5 mg, half tablet; once daily, Step 3), to 3.75 mg (bisoprolol 2.5 mg, 1.5 tablets once daily, Step 4), and to 5 mg (bisoprolol 2.5 mg, 2 tablets; or bisoprolol 5 mg, 1 tablet; once daily, Step 5).
Intervention: Bisoprolol (Drug)
Carvedilol group
Daily oral administration of carvedilol 1.25 mg, 1 tablet twice a day (after breakfast and supper) should be given (Step 1). If tolerability is confirmed by an investigator after administering 2.5 mg/day of carvedilol, the dose should be increased to 5 mg (carvedilol 2.5 mg, 1 tablet twice daily) (Step 2). In the same manner, the dose should be increased to 10 mg (carvedilol 2.5 mg, 2 tablets twice daily, Step 3), to 15 mg (carvedilol 2.5 mg, 3 tablets twice daily, Step 4), and to 20 mg (carvedilol 10 mg, 1 tablet twice daily, Step 5).
Intervention: Carvedilol (Drug)
Outcomes
Primary Outcomes
Tolerability: The probability that administered maintenance dose reaches the maximum (bisoprolol 5 mg/day, carvedilol 20 mg/day)
Time Frame: 48 weeks
Secondary Outcomes
- Efficacy: New York Heart Association (NYHA) Functional Classification(24 and 48 weeks)
- Efficacy: Left Ventricular Ejection Fraction (LVEF)(24 and 48 weeks)
- Efficacy: Heart rate(24 and 48 weeks)
- Efficacy: Plasma brain natriuretic peptide (BNP)(24 and 48 weeks)
- Safety: Deaths with cardiovascular causes(48 weeks)
- Efficacy: Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular End Systolic Volume (LVESV)(24 and 48 weeks)
- Safety: All deaths(48 weeks)
- Safety: Hospitalization for cardiovascular causes(48 weeks)
- Safety: Exacerbation of heart failure, resulting in hospitalization, and/or intensification of treatment (increase in dose of any diuretics, vasodilators or cardiotonics, in comparison with the dose-setting period), or administration of new drugs.(48 weeks)
- Safety: Deaths due to heart failure (pump-failure deaths, and deaths associated with exacerbation of heart failure)(48 weeks)
- Safety: Sudden deaths, including deaths due to arrhythmia(48 weeks)
- Safety: Deaths with non-cardiovascular causes(48 weeks)
- Safety: Adverse events(48 weeks)
- Safety: Changes in clinical laboratory test results(48 weeks)