Heart FailureNCT07379788
ARNI Combined With SGLT2 Inhibitors on Functional Mitral Regurgitation Remodeling
A study testing Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO] and Empagliflozin10Mg Tab in people with Heart Failure, run by Rehab Werida at 1 site in Saudi Arabia.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO] and Empagliflozin10Mg Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 1 siteSaudi Arabia
- Study dates
- 1 Jan 2025to 1 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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:
- ARNI Monotherapy Group: Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy.
- Combination Therapy Group: Patients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).
- Conditions
- Heart Failure
- Being tested
- Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO], Empagliflozin10Mg Tab
- Keywords
- Left atrial volume index (LAVI), Mitral Remodeling Index (MRIx), left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR)
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO]Drug
Also called Entresto
Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet without concomitant SGLT2 inhibitor therapy.
Empagliflozin10Mg TabDrug
Also called Empagliflozin10Mg plus Sacubitril/Valsartan 49 MG-51 MG Oral Tablet
Combination Therapy Group: Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).
| Study group | Role | What they receive |
|---|---|---|
| ARNI Monotherapy Group: | Placebo comparator | Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy. Receives: Drug: Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO] |
| Combination Therapy Group: | Active comparator | Patients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily). Receives: Drug: Empagliflozin10Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
LVEF %
Change in left ventricular ejection fraction percent
Measured: 6 months
Left Atrial Volume index (LAVI)
Change Left Atrial Volume index (LAVI)
Measured: 6 months
Mitral Remodeling Index
Change in Mitral Remodeling Index
Measured: 6 months
Peak GLS number
Change in Peak Global Longitudinal Strain
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2026
- Study start1 Jan 2025
- Primary completion28 Feb 2026
- Study completion1 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This was a randomized controlled study included 180 HFrEF patients (LVEF \<50%) with FMR, recruited from a tertiary cardiac referral center, who were randomized to receive either sacubitril/valsartan alone (n=90) or in combination with empagliflozin (n=90).
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rehab Werida
- Sponsor type
- University, hospital or other
- Collaborators
- Tanta University
- Responsible party
- Sponsor-investigator, Rehab Werida, Damanhour University
- Investigators
- Lamiaa Khedr, Ass Prof., Study director, Madina Cardiac Center, KSA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07379788
- Sponsor's protocol ID
- ARNI, SGLT2 Inhibitors & MRI
- Status last verified
- May 2026
- First submitted
- 23 Jan 2026
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
PubMed 25176015Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018 Oct;61(10):2108-2117. doi: 10.1007/s00125-018-4670-7. Epub 2018 Aug 22.
PubMed 30132036
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitral Remodeling Index: A Novel Composite Measure the Effect of ARNI Alone Versus ARNI Combined With SGLT2 Inhibitors on Functional Mitral Regurgitation Remodeling.
- ClinicalTrials.gov ID
- NCT07379788
- Acronym / sponsor ID
- ARNI, SGLT2 Inhibitors & MRI
- Conditions
- Heart Failure
- Keywords
- Left atrial volume index (LAVI), Mitral Remodeling Index (MRIx), left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Rehab WeridaUniversity, hospital or other
- Collaborators
- Tanta University
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 28 Feb 2026 (actual)
- Study completion
- 1 Mar 2026 (actual)
- First posted
- 30 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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:
- ARNI Monotherapy Group: Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy.
- Combination Therapy Group: Patients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This was a randomized controlled study included 180 HFrEF patients (LVEF <50%) with FMR, recruited from a tertiary cardiac referral center, who were randomized to receive either sacubitril/valsartan alone (n=90) or in combination with empagliflozin (n=90).
| Arm | Type | Receives |
|---|---|---|
| ARNI Monotherapy Group: | Placebo comparator | Drug: Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO]Patients receiving sacubitril/valsartan without concomitant SGLT2 inhibitor therapy. |
| Combination Therapy Group: | Active comparator | Drug: Empagliflozin10Mg TabPatients receiving sacubitril/valsartan in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO]Also: EntrestoPatients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet without concomitant SGLT2 inhibitor therapy. | Drug | ARNI Monotherapy Group: |
| Empagliflozin10Mg TabAlso: Empagliflozin10Mg plus Sacubitril/Valsartan 49 MG-51 MG Oral TabletCombination Therapy Group: Patients receiving Sacubitril/Valsartan 49 MG-51 MG Oral Tablet in combination with an SGLT2 inhibitor (empagliflozin 10 mg daily). | Drug | Combination Therapy Group: |
Primary outcome
LVEF %
Time frame: 6 months
Change in left ventricular ejection fraction percent
Left Atrial Volume index (LAVI)
Time frame: 6 months
Change Left Atrial Volume index (LAVI)
Mitral Remodeling Index
Time frame: 6 months
Change in Mitral Remodeling Index
Peak GLS number
Time frame: 6 months
Change in Peak Global Longitudinal Strain
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Background: PubMed 25176015McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
- Background: PubMed 30132036Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018 Oct;61(10):2108-2117. doi: 10.1007/s00125-018-4670-7. Epub 2018 Aug 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lamiaa Khedr, Ass Prof. study director
Madina Cardiac Center, KSA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sacubitril/Valsartan 49 MG-51 MG Oral Tablet [ENTRESTO] and Empagliflozin10Mg Tab in people with Heart Failure, run by Rehab Werida at 1 site in Saudi Arabia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LVEF % (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07379788, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.