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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Ventricular Dysfunction; Ventricular Remodeling
• Intervention / Treatment: Drug: SGLT2 inhibitor

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 Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: NADIA ASPROMONTE, Prof.; Phone Number: 00393477977895; Email: nadia.aspromonte@policlinicogemelli.it

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A. Gemelli IRCSS
      • Contact: NADIA ASPROMONTE, Prof.; Phone Number: 00393477977895; Email: nadia.aspromonte@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients affected by HFrEF on ARNI, eligible for glyphozine

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients affected by HFrEF on ARNI; patients affected by HFrEF in optimized medical therapy including ARNI, eligible for glyphozine	Drug: SGLT2 inhibitor; optimization of the medical therapy for heart failure with reduced ejection fraction with SGLT2 inhibitor, according to clinical guidelines; Other Names: Dapaglifozin, Empaglifozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: NADIA ASPROMONTE, Prof., Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Ventricular Dysfunction; Ventricular Remodeling; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: 5428

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No