Effects of the Sodium-glucose Cotransporter 2 Inhibitors+Sacubitril/Valsartan Therapy in Patients With HFrEF.

Heart Failure Clinical Trial

Official title:

Evaluation of the Effects of the Sodium-glucose Cotransporter 2 Inhibitors+Sacubitril/Valsartan Combined Therapy in Patients With HFrEF: an Echocardiographic Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05934071
• Other study ID #: 5428
• Status: Recruiting
• Start date: October 10, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: NADIA ASPROMONTE, Prof.
• Phone: 00393477977895
• Email: nadia.aspromonte[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to investigate the effects of combination therapy with ARNI and inhibitors of SGLT2 in patients affected by HFrEF.

The main questions it aims to answer are:

• What is the medium-long term impact of the ARNI + glyphozine combination therapy in terms of ventricular remodeling studied by speckle tracking echocardiography (GLS%) and by variation of volumetric indices and contractile function (LVEDV, LVEDD, FE%)?

• What is the medium-long term impact of the ARNI + glyphozine combination therapy in terms of variation of laboratory data indicative of heart failure (NT-pro-BNP)?

• What is the medium-long term impact of the ARNI + glyphozine combination therapy in terms of major cardiovascular events (MACVE)?

• What are the echocardiographic and laboratory parameters predictors of medium-long term major cardiovascular events (MACVE) and ventricular remodeling? Participants will undergo, at the time of enrollment and after approximately 3 and 12 months from the introduction of SGLT-2 inhibitor therapy, at clinical, echocardiographic and biohumoral investigations.

Description:

According to the 2021 ESC guidelines for heart failure, iSGLT2 has become the cornerstone of the treatment of heart failure with reduced ejection (HFrEF) fraction, with a class of recommendation IA (1).

However, the mechanisms of action of iSGLT2 remain still little known. In particular, if the combined therapy with ARNI and iSGLT2 may have an effect in terms of left ventricular remodeling evaluated by speckle tracking echocardiography (GLS%) in patients with HFrEF at a medium-long term (3-12 months) is still to be defined (primary objective).

Furthermore, our study will aim to evaluate the clinical and echocardiographic impact of the combined therapy with ARNI + iSGLT2 in terms of left ventricular remodeling evaluated through volumetric and contractile function indices (LVEDV, LVEDD, FE%) and in terms of variation of laboratory data suggestive of decompensated heart failure (NT-pro-BNP) in patients with HFrEF at a medium-long term follow-up (3-12 months) (secondary outcomes).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HFrEF on ARNI

• Ability to express written informed consent to participate in the study

Exclusion Criteria:

• Contraindication to glyphozine therapy (i.e., severe renal insufficiency with filtration estimated glomerular <30ml/min/m2 or history of recurrent urinary tract infections);

• Comorbidities with expected survival of less than 1 year;

• Limited or legal inability to give written informed consent

Related Conditions & MeSH terms

• Heart Failure
• Ventricular Dysfunction
• Ventricular Remodeling

Intervention

Drug:
• SGLT2 inhibitor
optimization of the medical therapy for heart failure with reduced ejection fraction with SGLT2 inhibitor, according to clinical guidelines

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario A. Gemelli IRCSS	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ventricular remodeling studied by speckle tracking echocardiography	Evaluation of the medium-long term impact of the ARNI + glyphozine combination therapy in terms of ventricular remodeling studied through speckle tracking echocardiography and evaluated in terms of global longitudinal strain values (GLS%)	3-12 months
Secondary	variation of volumetric indices and contractile function	Evaluation of the medium-long term impact of the ARNI + glyphozine combination therapy in terms of ventricular remodeling studied through echocardiography and evaluated as LV volumes (end diastolic volumes-ml/m2 and and systolic volumes ml/m2) and LV function (left ventricular ejection fraction-%) indices	3-12 months
Secondary	variation of laboratory data indicative of heart failure (NT-pro-BNP)	Evaluation of the medium-long term impact of the ARNI + glyphozine combination therapy in terms of variation of laboratory data indicative of heart failure (N-terminal pro B type natriuretic peptide-pg/mL)	3-12 months
Secondary	major cardiovascular events (MACVE)	Evaluation of the medium-long term impact of the ARNI + glyphozine combination therapy in terms of major adverse cardiovascular events (composite endpoint of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke)	3-12 months
Secondary	echocardiographic and laboratory parameters predictors of medium-long term major cardiovascular events (MACVE) and ventricular remodeling	Identification of the echocardiographic and laboratory parameters predictors of medium-long term major cardiovascular events (MACVE) and ventricular remodeling in terms of variation of LV volumes (end diastolic volumes-ml/m2 and and systolic volumes ml/m2) and LV function (left ventricular ejection fraction-%) indices	3-12 months