Clinical trial NCT05849766: Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
Official title: Effect of Dapagliflozin on Cardiac Structure in Patients with Left Ventricular Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dilated Cardiomyopathy
Lead sponsor: October 6 University
Sponsor class: OTHER
Collaborators: name: National Heart Institute, Egypt
name: University of Florida
First posted: 2023-05-09
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median / Mean of effective regurgitant orifice area (EROA) of functional mitral regurgitation in patient echocardiographic measures
timeFrame: 6 months
Secondary outcomes:
measure: Median / Mean of Left ventricle Ejection Fraction (LVEF) of patients in patient echocardiographic measures
timeFrame: 6 months
measure: Median / Mean of Natriuretic peptide concentration (ProBNP) in serum of patients
timeFrame: 6 months
Other outcomes:
Locations:
city: Banī Suwayf
country: Egypt
facility: Beni-suef University
Study officials:
affiliation: October 6 University
name: Ahmed Essam Abou Warda
role: PRINCIPAL_INVESTIGATOR
References: