ARNI Combined With SGLT2 Inhibitors on Functional Mitral Regurgitation Remodeling

May 29, 2026 updated by: Rehab Werida

Mitral Remodeling Index: A Novel Composite Measure the Effect of ARNI Alone Versus ARNI Combined With SGLT2 Inhibitors on Functional Mitral Regurgitation Remodeling.

This study aimed to compare the effects of ARNI monotherapy versus combined ARNI and SGLT2 inhibitor therapy on Mitral Remodeling Index (MRIx) and Functional mitral regurgitation (FMR) remodeling in patients with heart failure with reduced ejection fraction (HFrEF).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a study conducted at Madinah Cardiac Center (MCC), Saudi Arabia, a tertiary referral center with a high-volume heart-failure unit and advanced echocardiographic services. Consecutive patients with chronic heart failure with reduced ejection fraction (HFrEF) and functional mitral regurgitation (FMR) were enrolled between [January 2025] and [December 2025].

Eligible patients were on sacubitril/valsartan (ARNI), either as monotherapy or in combination with a sodium-glucose cotransporter-2 (SGLT2) inhibitor, according to contemporary heart failure guidelines and treating physician discretion.

The study protocol conformed to the principles of the Declaration of Helsinki and was approved by the local institutional ethics committee; Madinah Cardiac Center before the beginning of the study.

• Treatment Groups

Patients were stratified into two groups based on pharmacological therapy:

  1. ARNI Monotherapy Group: Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy.
  2. Combination Therapy Group: Patients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

• Treatment Groups

Patients were stratified into two groups based on pharmacological therapy:

  1. ARNI Monotherapy Group: Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet without concomitant SGLT2 inhibitor therapy.
  2. Combination Therapy Group: Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).

Sacubitril/valsartan was initiated and up titrated to the maximally tolerated dose according to guideline recommendations (13). SGLT2 inhibitors were prescribed at standard approved doses. Background heart failure therapy, including beta-blockers and mineralocorticoid receptor antagonists, was maintained whenever clinically feasible.

Description

Inclusion Criteria:

  • age ≥18 years;
  • left ventricular ejection fraction (LVEF) <50%;
  • Presence of functional mitral regurgitation (mild, moderate, or severe) on transthoracic echocardiography; and
  • stable sinus rhythm or controlled atrial fibrillation.

Exclusion Criteria:

  • primary (degenerative or rheumatic) mitral valve disease,
  • prior mitral valve surgery or transcatheter intervention,
  • acute decompensated heart failure within four weeks,
  • significant primary valvular disease other than FMR,
  • severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m²),
  • inadequate echocardiographic image quality.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: ARNI Monotherapy Group:
Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy.
Drug: Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO]
Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet without concomitant SGLT2 inhibitor therapy.
Other Names:
  • Entresto
Active Comparator: Combination Therapy Group:
Patients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).
Drug: Empagliflozin10Mg Tab
Combination Therapy Group: Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).
Other Names:
  • Empagliflozin10Mg plus Sacubitril/Valsartan 49 MG-51 MG Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LVEF %
Time Frame: 6 months
Change in left ventricular ejection fraction percent
6 months
Left Atrial Volume index (LAVI)
Time Frame: 6 months
Change Left Atrial Volume index (LAVI)
6 months
Mitral Remodeling Index
Time Frame: 6 months
Change in Mitral Remodeling Index
6 months
Peak GLS number
Time Frame: 6 months
Change in Peak Global Longitudinal Strain
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rehab Werida

Collaborators

Tanta University

Investigators

  • Study Director: Lamiaa Khedr, Ass Prof., Madina Cardiac Center, KSA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Actual)

February 28, 2026

Study Completion (Actual)

March 1, 2026

Study Registration Dates

First Submitted

January 23, 2026

First Submitted That Met QC Criteria

January 23, 2026

First Posted (Actual)

January 30, 2026

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARNI, SGLT2 Inhibitors & MRI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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