Clinical trial NCT06260059: Efficacy of Sodium Glucose Transporter Inhibitor (SGLT2I) in Adult Patients with Congenital Heart Disease
Official title: Efficacy of Sodium Glucose Transporter Inhibitor (SGLT2i) in Adult Patients with Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Adult Congenital Heart Disease
Heart Failure
Keywords: congenital heart disease
reduced exercise capacity
decreased cardiac function
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: The Pittsburgh Foundation
First posted: 2024-02-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group 1: Empagliflozin 10 MG daily Group 2: Placebo
Primary purpose: TREATMENT

Brief summary: The goal of the study is to investigate the feasibility and benefit of novel guideline-directed heart failure therapy drug Empagliflozin (Jardiance) for adult patients with congenital heart disease (ACHD).

Detailed description: As CHD adolescents transition to adulthood, it is becoming evident that in addition to their structural cardiac abnormalities, they also have an intrinsic disease of the heart muscle which manifests as abnormal heart rhythm (arrhythmia) and decreased function (heart failure).

The lifesaving cardiac surgeries during childhood can also contribute to this dysfunction (cardiomyopathy). Hence, patients with CHD require multiple interventions and close clinical follow-up throughout their life. Currently, there are over 2.5 million CHD patients in the U.S. alone, and an additional 40,000 babies are born with CHD every year. Up to 50% of these patients require inpatient hospital care at some point due to their cardiomyopathy.

High-risk ACHD patients do not receive treatment until they present with heart failure or arrhythmia, at which time there is significant evidence of myocardial disease and dysfunction.

Empagliflozin (Jardiance) is an FDA-approved drug that significantly reduces hospitalization risk and cardiovascular death in adult patients with non-CHD heart failure. Studies show that Empagliflozin protects the heart from inflammation, and preliminary evaluation of Empagliflozin in symptomatic ACHD patients showed improved cardiac function and a reduction in heart failure including decreased shortness of breath and increased functional capacity. Empagliflozin as a preventative therapy may delay the onset of comorbidities by reducing inflammation in ACHD patients.

The study hypothesis is that the administration of once-a-day oral Jardiance (Empagliflozin) medication for one year reduces arrhythmia and cardiomyopathy and lowers serum circulating inflammatory factors and improves neurocognitive outcomes in susceptible ACHD patients.

1. Does Empagliflozin 10 milligrams (MG) improve cardiac function in ACHD patients
2. Does Empagliflozin 10 milligrams (MG) improve functional status in ACHD patients

Eligibility criteria: Inclusion Criteria:

* Diagnoses of Congenital Heart Disease
* Age 18+
* ACHD level of structural complexity II or III
* Recent (\<6 months) decrease in systemic Ejection Fraction (confirmed by cardiac Echocardiogram, Computed Tomography or cMRI) to EF \< 60%
* Recent decrease in systemic ejection fraction confirmed by cardiac Echo, CT or MRI by \> 5% in the last 6 months or less.
* Must be able to complete neurocognitive assessments on a handheld computer.

Exclusion Criteria:

* Diagnosed with Diabetes
* Contraindication to Jardiance/Entresto or any heart failure medication (per guideline-directed therapy, 2022).
* Previous therapy with Jardiance at \<4 weeks
* Glomerular Filtration Rate \<20
* Pregnancy, breastfeeding, or planning to become pregnant in the coming year
* History of liver disease - including non-alcoholic fatty liver disease (NAFLD) and cirrhosis
* History of inborn error(s) of metabolism (including but is not exclusive of Glycogen storage disease type 1)
* Glucose-galactose malabsorption, familial hyperinsulinism, maple syrup urine disease,
* Gaucher disease,
* Tay-Sachs disease,
* Mucolipidosis IV,
* Niemann-Pick disease,
* Type A mitochondrial disease,
* Metabolic disorders related to glucose metabolism

Primary outcomes:
measure: Change in Ejection fraction (EF)
timeFrame: Change from baseline in ejection fraction at 1-year
measure: Change in Myocardial characteristics (T1 mapping of cMRI)
timeFrame: Change from baseline in T1 mapping at 1-year
measure: Change in Myocardial characteristics (Global strain on MRI)
timeFrame: Change from baseline of global strain on MRI at 1 year
measure: Change in Myocardial characteristics (Global strain on echocardiogram)
timeFrame: Change from baseline of global strain on echocardiogram at 1 year
measure: Change in functional exercise capacity of participants.
timeFrame: Change from baseline of exercise capacity at 1-year
measure: Number of Participants Hospitalized for Cardiac Reasons or heart transplantation
timeFrame: Cardiac hospitalizations or transplantation at 1 year.
measure: Number of Deaths
timeFrame: Number of deaths at 1 year
Secondary outcomes:
measure: Change in inflammatory serum biomarkers
timeFrame: Change from baseline of serum biomarkers at 1-year
measure: Change in functional Neuropsychological Testing
timeFrame: Change from baseline of neuropsychological testing at 1-year
measure: Change in New York Heart Association (NYHA) Class
timeFrame: Change from baseline of NYHA Class at 1-year.
measure: Change Patient-Reported Outcomes Measurement Information System (PROMIS)
timeFrame: Change from baseline of PROMIS composite score at 1 year
measure: Change in Kansas City Cardiomyopathy (KCCQ)
timeFrame: Change from baseline of KCCQ score at 1 year
measure: Change in Neuro-QOL
timeFrame: Change from baseline of Neuro-QOL score at 1 year
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee Women's Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Presbyterian Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Assistant Professor
name: Anita Saraf, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: