Effect of Dapagliflozin on Secondary Mitral Regurgitation

Sponsor

October 6 University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05849766

Collaborator

Beni-Suef University (Other), National Heart Institute, Egypt (Other)

150

Enrollment

Location

Arms

12.2

Anticipated Duration (Months)

12.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A significant reduction in the incidence of CV death or hospitalization for HF has been observed in randomized trials investigating the CV benefit of Dapagliflozin. Mechanistic investigations are required to interpret the positive clinical effects of Dapagliflozin on heart structure and valvular regurgitation.

Condition or Disease	Intervention/Treatment	Phase
Dilated Cardiomyopathy	Drug: Dapagliflozin Farxiga® Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®	Phase 3

Detailed Description

A functional mitral regurgitation (MR) occurs when the mitral valve (MV) becomes tethered due to abnormal LV remodelling in individuals with heart failure (HF) and left ventricular (LV) dilatation.

The primary treatment for HF is medical, and it is based on established guidelines, as LV failure is the most common cause of secondary functional MR. Standard medical therapy for patients with functional MR, including beta blockers, ACE inhibitors, and angiotensin receptor blockers (ARB), does not reduce the morbidity or mortality associated with these conditions.

Similar to the neprilysin inhibitor, which promotes sodium excretion and has vasodilatory effects via relaxing blood vessels, Dapagliflozin reduce cardiac preload and afterload by inducing natriuresis and reducing arterial stiffness. Effects on blood pressure reduction and weight loss may also positively affect left ventricular (LV) remodelling.

Using echocardiography, researchers hope to test the hypothesis that dapagliflozin improves MR in patients with functional MR due to LV dysfunction. This hypothesis is based on studies showing the beneficial effects of Dapagliflozin on LV modelling.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Dapagliflozin on Secondary Mitral Regurgitation in Patients With Left Ventricular Dysfunction

Actual Study Start Date :

Apr 27, 2023

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control Group 1 received only standard therapy ACE/ ARB, BB, and diuretics	Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone® Ramipril 10 mg once daily, carvedilol 6.25 mg twice daily and spironolactone 25 once daily Other Names: Tritace, Carvid, Aldactone
Experimental: Interventional Group 2 received dapagliflozin 10 mg once daily in addition to standard therapy ACE/ ARB, BB, and diuretics	Drug: Dapagliflozin Farxiga® Dapagliflozin 10 mg once daily Other Names: Forxiga

Arm

Intervention/Treatment

Placebo Comparator: Control

Group 1 received only standard therapy ACE/ ARB, BB, and diuretics

Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®

Ramipril 10 mg once daily, carvedilol 6.25 mg twice daily and spironolactone 25 once daily

Other Names:

Tritace, Carvid, Aldactone

Experimental: Interventional

Group 2 received dapagliflozin 10 mg once daily in addition to standard therapy ACE/ ARB, BB, and diuretics

Drug: Dapagliflozin Farxiga®

Dapagliflozin 10 mg once daily

Other Names:

Forxiga

Outcome Measures

Primary Outcome Measures

Median / Mean of effective regurgitant orifice area (EROA) of functional mitral regurgitation in patient echocardiographic measures [6 months]
Change in median / mean of EROA before and after drug administration

Secondary Outcome Measures

Median / Mean of Natriuretic peptide concentration (ProBNP) in serum of patients [6 months]
Change in median / mean of ProBNP before and after drug administration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Outpatients ≥ 18 years of age
Dilated LV with a reduced ejection fraction and secondary functional MR
NYHA functional class II or III
Moderate to Severe MR which lasted > 6 months under medical treatment with a β-blocker and an ACE inhibitor (or ARB)

Exclusion Criteria:

Current use or prior use of Dapagliflozin
Current acute heart failure or prior admission with acute decompensated heart failure in 6 months before entry to study
NYHA functional class IV
Chronic renal impairment with GFR < 30 mL/min/1.73m2
Pregnant or lactating women
History of allergy to Dapagliflozin