Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction

Phase 3

Completed

• Conditions: Dilated Cardiomyopathy
• Interventions: Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®; Drug: Dapagliflozin Farxiga®

• Registration Number: NCT05849766
• Lead Sponsor: October 6 University

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.

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 Timeline

• Study Start: 2023-04-27
• Study First Submitted: 2023-04-27
• Study First Submitted QC: 2023-05-07
• Study First Posted: 2023-05-09
• Primary Completion: 2024-05-01
• Study Completion: 2024-09-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-14
• Last Update Posted: 2024-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®	Group 1 received only standard therapy ACE/ ARB, BB, and diuretics
Interventional	Dapagliflozin Farxiga®	Group 2 received dapagliflozin 10 mg once daily in addition to standard therapy ACE/ ARB, BB, and diuretics

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Median / Mean of Left ventricle Ejection Fraction (LVEF) of patients in patient echocardiographic measures	6 months	Change in median / mean of LVEF before and after drug administration
Median / Mean of Natriuretic peptide concentration (ProBNP) in serum of patients	6 months	Change in median / mean of ProBNP before and after drug administration

Trial Locations

Locations (1)

Beni-suef University; 🇪🇬 Banī Suwayf, Egypt