Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
HFrEF, Carvedilol, Slow Release, NT-proBNP
Brief summary
Assessment of clinical effect and treatment quality of immediate release carvedilol (IR) versus slow release carvedilol (SR) in patients with HFrEF
Detailed description
The SLOW-HF trial is a phase 4, randomized, open label, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in patients with heart failure with reduced ejection fraction. Patients with stable HFrEF will be randomly assigned (1:1) to carvedilol SR group (160 patients) and carvedilol IR group (160 patients). After randomization, patients will be followed for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the frequency of NT-proBNP increment \>10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.
Interventions
DRUGCarVeDilol-SR (Slow Release)
patients will receive slow-release carvedilol (SR) once daily
DRUGCarvedilol IR (Immediate Release)
patients will receive immediate release carvedilol (IR) twice daily
Sponsors
Chong Kun Dang Pharmaceutical Corp.
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
PROBE and NON-INFERIORITY DESIGN for Slow Release CarVeDilol-SR to Rapid Release Carvedilol-IR
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least or more than 20-years-old male and female 2. Confirmed left ventricular ejection fraction ≤40% by echocardiography within pre-analytical 6 months 3. NT-proBNP level ≥ 125 pg/ml or BNP level ≥ 35 pg/ml within pre-analytical 3 months 4. Clinically stable patient without evidence of congestion or extracellular fluid retention; those could be candidate of β-blockers 5. Patients providing written informed consent
Exclusion criteria
1. Systolic blood pressure at sitting position \< 90mmHg or resting heart rate \< 50 /min at screening 2. Patient has a contraindication to β-blockers 3. Patient who are expected to take another β-blocker after randomization 4. Cardiovascular diseases * Ischemic heart disease (unstable angina, myocardial infarction) within 1 month * Hypertrophic cardiomyopathy * Cor pulmonale * Hemodynamically significant stenosis of aorta, aortic valve, or mitral valve * any acute myocardial infarction with complication 5. Severe cerebrovascular accident (for example, ischemic stroke or cerebral hemorrhage) pre-analytical within 6 months 6. Glottis edema, allergic rhinitis, respiratory diseases with bronchospasm such as asthma and chronic obstructive lung disease 7. Peripheral vascular disease (for example, Raynaud syndrome, intermittent claudication) 8. Patients who need vasopressor due to prominent volume retention/overload 9. Moderate to Severe retinopathy (for example, retinal hemorrhage, visual disturbance, retinal microaneurysm within 6 months) 10. Impaired renal function (Serum creatinine ≥ 2.5 mg/dL) or hepatic function (AST or ALT ≥ 3 x ULM) 11. Patients in clinical status that can significantly influence on absorption, distribution, metabolism, and secretion of drugs for clinical trial * history of major gastrointestinal surgery, such as gastrectomy or gastric bypass surgery * inflammatory bowel disease within 12 months * current gastric ulcer, pancreatic function abnormality including pancreatitis, gastrointestinal/rectal bleeding which demand treatment * current urologic stenosis or obstruction which demand treatment 12. Confirmed or suspected drug/alcohol abuse within 6 months 13. Pregnant or lactating women, suspected pregnant women or lactating women 14. Chronic inflammatory diseases which demand anti-inflammatory treatment 15. Hypersensitivity to carvedilol 16. Malignant disease including lymphoma and leukemia within 5 years 17. Patients who were prescribed other medication for any clinical trials pre-analytical within 28 days 18. Patients who are predicted to have prolonged hospital days due to other medical problems other than chronic heart failure (for example, femur neck fracture) 19. Patients who are considered as inappropriate to participate in the clinical trial by testers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NT-proBNP | 6 months | Change of NT-proBNP from baseline to 6 months after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Death | 6 months | Difference in all-cause deaths between the groups during clinical follow-up |
| Hospitalization | 6 months | Difference in hospitalization for heart failure between the groups during clinical follow-up |
| Blood Pressure | 6 months | Difference in blood pressure change between the groups during clinical follow-up |
| Dyspnea | 6 months | Differences in dyspnea measured with visual analogue scale between the groups during clinical follow-up |
| Drug compliance | 6 months | Differences in drug compliance measured with 'pill-count' between the groups during clinical follow-up |
Countries
South Korea
Outcome results
None listed