Immediate Release Versus Slow Release Carvedilol in Heart Failure

Study Overview
=================
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.

Official Title
-----------------
Assessment of Clinical Effect and Treatment Quality of Rapid Release Carvedilol Versus SLOW Release Carvedilol-SR in HEART FAILURE Patient (SLOW-HF): A Prospective Randomized, Open-label, Multicenter Study

Conditions
-----------------
Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
-----------------
* Drug: CarVeDilol-SR (Slow Release)
* Drug: Carvedilol IR (Immediate Release)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: At least or more than 20-years-old male and female Confirmed left ventricular ejection fraction ≤40% by echocardiography within pre-analytical 6 months NT-proBNP level ≥ 125 pg/ml or BNP level ≥ 35 pg/ml within pre-analytical 3 months Clinically stable patient without evidence of congestion or extracellular fluid retention; those could be candidate of β-blockers Patients providing written informed consent Exclusion Criteria: Systolic blood pressure at sitting position < 90mmHg or resting heart rate < 50 /min at screening Patient has a contraindication to β-blockers Patient who are expected to take another β-blocker after randomization 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 Severe cerebrovascular accident (for example, ischemic stroke or cerebral hemorrhage) pre-analytical within 6 months Glottis edema, allergic rhinitis, respiratory diseases with bronchospasm such as asthma and chronic obstructive lung disease Peripheral vascular disease (for example, Raynaud syndrome, intermittent claudication) Patients who need vasopressor due to prominent volume retention/overload Moderate to Severe retinopathy (for example, retinal hemorrhage, visual disturbance, retinal microaneurysm within 6 months) Impaired renal function (Serum creatinine ≥ 2.5 mg/dL) or hepatic function (AST or ALT ≥ 3 x ULM) 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 Confirmed or suspected drug/alcohol abuse within 6 months Pregnant or lactating women, suspected pregnant women or lactating women Chronic inflammatory diseases which demand anti-inflammatory treatment Hypersensitivity to carvedilol Malignant disease including lymphoma and leukemia within 5 years Patients who were prescribed other medication for any clinical trials pre-analytical within 28 days Patients who are predicted to have prolonged hospital days due to other medical problems other than chronic heart failure (for example, femur neck fracture) Patients who are considered as inappropriate to participate in the clinical trial by testers

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: PROBE and NON-INFERIORITY DESIGN for Slow Release CarVeDilol-SR to Rapid Release Carvedilol-IR
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carvedilol IR (Immediate Release)<br>Carvedilol IR 3.125mg, 6.25mg, 12.5mg, 25mg twice daily p.o. for 6 months | Drug: Carvedilol IR (Immediate Release)<br>* patients will receive immediate release carvedilol (IR) twice daily<br>|
| Experimental: CarVeDilol-SR (Slow Release)<br>CarVeDilol-SR 8mg, 16mg, 32mg, 64mg once daily p.o. for 6 months | Drug: CarVeDilol-SR (Slow Release)<br>* patients will receive slow-release carvedilol (SR) once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-proBNP | Change of NT-proBNP from baseline to 6 months after randomization | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Death | Difference in all-cause deaths between the groups during clinical follow-up | 6 months | 
| Hospitalization | Difference in hospitalization for heart failure between the groups during clinical follow-up | 6 months | 
| Blood Pressure | Difference in blood pressure change between the groups during clinical follow-up | 6 months | 
| Dyspnea | Differences in dyspnea measured with visual analogue scale between the groups during clinical follow-up | 6 months | 
| Drug compliance | Differences in drug compliance measured with 'pill-count' between the groups during clinical follow-up | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carvedilol, Slow Release, NT-proBNP, HFrEF