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

Phase 4

• Conditions: Heart Failure With Reduced Ejection Fraction HFrEF
• Interventions: Drug: Carvedilol

• Registration Number: NCT05179070
• Lead Sponsor: Universitas Sebelas Maret

Brief Summary

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

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).

Study Timeline

• Study Start: 2021-09-10
• Study First Submitted: 2021-11-17
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-20
• Last Update Submitted: 2021-12-20
• Study First Posted: 2022-01-05
• Last Update Posted: 2022-01-05
• Primary Completion: 2022-02-28
• Study Completion: 2022-03-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 26

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
UpTitration	Carvedilol	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
Control	Carvedilol	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Major Adverse Cardiac Events	1 month	All cause cardiac rehospitalization

Trial Locations

Locations (1)

Universitas Sebelas Maret Hospital; 🇮🇩 Sukoharjo, Central Of Java, Indonesia