Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial.
BACKGROUND
Carvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF.


METHODS/DESIGN
Patients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with 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.


DISCUSSIONS
The SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF.


TRIAL REGISTRATION
ClinicalTrials.gov, ID: NCT03209180 . Registered on 6 July 2017.
['Choi|Dong-Ju|DJ|', 'Park|Chan Soon|CS|', 'Park|Jin Joo|JJ|http://orcid.org/0000-0001-9611-1490', 'Lee|Hae-Young|HY|', 'Kang|Seok-Min|SM|', 'Yoo|Byung-Su|BS|', 'Jeon|Eun-Seok|ES|', 'Hong|Seok Keun|SK|', 'Shin|Joon-Han|JH|', 'Kim|Myung-A|MA|', 'Park|Dae-Gyun|DG|', 'Kim|Eung-Ju|EJ|', 'Hong|Soon-Jun|SJ|', 'Kim|Seok Yeon|SY|', 'Kim|Jae-Joong|JJ|']
D000319:Adrenergic beta-Antagonists D015415:Biomarkers D000077261:Carvedilol D017327:Clinical Trials, Phase IV as Topic D003692:Delayed-Action Preparations D004339:Drug Compounding D005260:Female D006333:Heart Failure D006801:Humans D008297:Male D015337:Multicenter Studies as Topic D020097:Natriuretic Peptide, Brain D010446:Peptide Fragments D011446:Prospective Studies D016032:Randomized Controlled Trials as Topic D020127:Recovery of Function D056910:Republic of Korea D013318:Stroke Volume D013997:Time Factors D016896:Treatment Outcome D016277:Ventricular Function, Left
Slow release Carvedilol Clinical efficacy NT-proBNP Heart failure with reduced ejection fraction Immediate release