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

October 6 University

Status and phase: Completed; Phase 3

Conditions: Dilated Cardiomyopathy

Treatments: Drug: Dapagliflozin Farxiga®; Drug: Ramipril Tritace®, Carvedilol Carvid®,and Spironolactone Aldactone®

Study type: Interventional

Funder types: Other

Identifiers

NCT05849766

IHC00044

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

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

Treatment:

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

Interventional

Experimental group

Description:

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

Treatment:

Drug: Dapagliflozin Farxiga®