Clinical trial NCT05179070: Effect of Carvedilol Rapid Up-Titration in Patients With Heart Failure With Reduced Ejection Fraction
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure With Reduced Ejection Fraction HFrEF
Keywords: HFrEF
Carvedilol
Rapid UpTitration
Heart Failure
Lead sponsor: Universitas Sebelas Maret
Sponsor class: OTHER
First posted: 2022-01-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Improvements of Biomolecular Parameters
timeFrame: 1 month
measure: Improvements of Clinical Parameters
timeFrame: 1 month
measure: Improvements of Echocardiography Parameters
timeFrame: 1 month
Secondary outcomes:
measure: Major Adverse Cardiac Events
timeFrame: 1 month
Other outcomes:
Locations:
city: Sukoharjo
country: Indonesia
facility: Universitas Sebelas Maret Hospital
state: Central Of Java
Study officials:
affiliation: Universitas Sebelas Maret
name: Habibie Arifianto, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wolfe NK, Mitchell JD, Brown DL. The independent reduction in mortality associated with guideline-directed medical therapy in patients with coronary artery disease and heart failure with reduced ejection fraction. Eur Heart J Qual Care Clin Outcomes. 2021 Jul 21;7(4):416-421. doi: 10.1093/ehjqcco/qcaa032.
citation: Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017 Aug 8;70(6):776-803. doi: 10.1016/j.jacc.2017.04.025. Epub 2017 Apr 28. No abstract available.
citation: Martinez-Selles M, Datino T, Alhama M, Barrueco N, Castillo I, Fernandez-Aviles F. Rapid carvedilol up-titration in hospitalized patients with left ventricular systolic dysfunction--data from the Carvedilol in Hospital: Up-titration Limits after Acute Patients Admission registry. J Cardiovasc Med (Hagerstown). 2010 May;11(5):352-8. doi: 10.2459/JCM.0b013e328334f48b.
citation: Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592. Epub 2016 May 20. No abstract available.