Effect of Carvedilol Rapid Up-Titration in Patients With Heart Failure With Reduced Ejection Fraction

Study Overview
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Brief Summary
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Guidelines-directed medical therapy has improved dramatically outcomes in heart failure with reduced ejection fraction (HFrEF) patients. Beta-blockers have the most beneficial effects on all caused mortality and rehospitalization on HFrEF, but unfortunately, since the discovery of beta-blocker therapy in HFrEF, there was no change in the way of titration, start low go slow, which resulted in difficulties in reaching optimal doses for some patients.

Detailed Description
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This study is a randomized controlled trial, single-center study in HFrEF patients, that held in Universitas Sebelas Maret Hospital, Central Java, Indonesia. The investigators divided 26 HFrEF patients consecutively into two groups, the first is the rapid up-titration group, which will get carvedilol up-titration every day, 3.125mg twice daily on the first day, 6.125mg twice daily on the second day, 12.5mg twice daily on the third day and 25mg twice daily on the fourth day consecutively. And the second group will have carvedilol titration according to established guidelines on Heart Failure, start 3.125mg twice daily, and up titrated every 2 weeks. Every patient will be checked for IL-6, TNF-α, NT-ProBNP, MDA, left ventricular Ejection Fraction, six minutes walking test, and Kansas City Cardiomyopathy Questionnaire on day 1, pre-discharge, and one month after hospitalization. The study was approved by the university ethics committee. The clinical parameters evaluated at admission were analyzed using variable comparative with Shapiro Wilk or one-way ANOVA, with three intervals analysis using repeated ANOVA (p<0.05).

Official Title
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The Effect of Carvedilol Rapid Up-Titration in Patients With Heart Failure With Reduced Ejection Fraction (Biomolecular and Clinical Study on IL-6, TNF-α, NT-ProBNP, MDA, LVEF, 6MWT, and KCCQ)

Conditions
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Heart Failure With Reduced Ejection Fraction HFrEF

Intervention / Treatment
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* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute heart failure patient with reduced ejection fraction in Universitas Sebelas Maret Hospital with naive betablocker therapy Age >18 years old Initial Heart Rate > 50 bpm Exclusion Criteria: Cardiogenic Shock Septicaemia High degree AV Block or on pace maker History of beta blocker intolerance Reactive Pulmonary disease Severe Peripheral artery disease Creatinine level > 2.5 mg/dl Potassium serum >5 mmol/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Devided into 2 groups. The first is the rapid up-titration group, which will get carvedilol up-titration every day, 3.125mg twice daily on the first day, 6.125mg twice daily on the second day, 12.5mg twice daily on the third day and 25mg twice daily on the fourth day consecutively. And the second group will have carvedilol titration according to established guidelines on Heart Failure, start 3.125mg twice daily, and up titrated every 2 weeks
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UpTitration<br>the first is the rapid up-titration group, which will get carvedilol up-titration every day, 3.125mg twice daily on the first day, 6.125mg twice daily on the second day, 12.5mg twice daily on the third day and 25mg twice daily on the fourth day consecutively | Drug: Carvedilol<br>* the first is the rapid up-titration group, which will get carvedilol up-titration every day, 3.125mg twice daily on the first day, 6.125mg twice daily on the second day, 12.5mg twice daily on the third day and 25mg twice daily on the fourth day consecutively. And the second group will have carvedilol titration according to established guidelines on Heart Failure, start 3.125mg twice daily, and up titrated every 2 weeks<br>* Other names: Vblock;|
| Active Comparator: Control<br>And the second group will have carvedilol titration according to established guidelines on Heart Failure, start 3.125mg twice daily, and up titrated every 2 weeks | Drug: Carvedilol<br>* the first is the rapid up-titration group, which will get carvedilol up-titration every day, 3.125mg twice daily on the first day, 6.125mg twice daily on the second day, 12.5mg twice daily on the third day and 25mg twice daily on the fourth day consecutively. And the second group will have carvedilol titration according to established guidelines on Heart Failure, start 3.125mg twice daily, and up titrated every 2 weeks<br>* Other names: Vblock;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvements of Biomolecular Parameters | IL-6 in pg/ml, TNF-α in pg/ml, NT-ProBNP in pg/ml, Malondyaldehide nmol/ml | 1 month | 
| Improvements of Clinical Parameters | Kansas City Cardiomyopathy Questionnaire (KCCQ) scores are scaled 0-100 (the higher score indicates a better condition) and 6 Minutes Walking Test in meters | 1 month | 
| Improvements of Echocardiography Parameters | LVEF | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events | All cause cardiac rehospitalization | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HFrEF, Carvedilol, Rapid UpTitration, Heart Failure