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

Recruiting

• Conditions: Ventricular Dysfunction; Heart Failure; Ventricular Remodeling
• Interventions: Drug: SGLT2 inhibitor

• Registration Number: NCT05934071
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief 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.

Detailed 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).

Study Timeline

• Study Start: 2022-10-10
• Study First Submitted: 2023-03-03
• Status Verified: 2023-06
• Study First Submitted QC: 2023-06-28
• Last Update Submitted: 2023-06-28
• Study First Posted: 2023-07-06
• Last Update Posted: 2023-07-06
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
patients affected by HFrEF on ARNI	SGLT2 inhibitor	patients affected by HFrEF in optimized medical therapy including ARNI, eligible for glyphozine

Primary Outcome Measures

Name	Time	Method
ventricular remodeling studied by speckle tracking echocardiography	3-12 months	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%)

Secondary Outcome Measures

Name	Time	Method
major cardiovascular events (MACVE)	3-12 months	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)
variation of volumetric indices and contractile function	3-12 months	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
variation of laboratory data indicative of heart failure (NT-pro-BNP)	3-12 months	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)
echocardiographic and laboratory parameters predictors of medium-long term major cardiovascular events (MACVE) and ventricular remodeling	3-12 months	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

Trial Locations

Locations (1)

Fondazione Policlinico Universitario A. Gemelli IRCSS; 🇮🇹 Roma, RM, Italy