Effect of Dapagliflozin on Secondary Mitral Regurgitation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: Dapagliflozin Farxiga®
* Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median / Mean of effective regurgitant orifice area (EROA) of functional mitral regurgitation in patient echocardiographic measures | Change in median / mean of EROA before and after drug administration | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median / Mean of Natriuretic peptide concentration (ProBNP) in serum of patients | Change in median / mean of ProBNP before and after drug administration | 6 months |