Efficacy of Sodium Glucose Transporter Inhibitor (SGLT2i) in Adult Patients With Congenital Heart Disease
Trial Snapshot
- Phase
- Phase 4
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 6
- Primary Endpoint
- Change in Myocardial characteristics (T1 mapping of cMRI)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnoses of Congenital Heart Disease
- •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
Arms & Interventions
Placebo
Placebo for 1 year
Intervention: Placebo (Drug)
Empagliflozin 10 MG
Empagliflozin 10 mg daily will be administered for 1 year. The patient and the PI will be blinded (unaware) of the group they are assigned to.
Intervention: Empagliflozin 10 MG (Drug)
Outcomes
Primary Outcomes
Change in Myocardial characteristics (T1 mapping of cMRI)
Time Frame: Change from baseline in T1 mapping at 1-year
Cardiac Magnetic Resonance Imaging (cMRI) without contrast will be used to measure myocardial characteristics
Change in Myocardial characteristics (Global strain on echocardiogram)
Time Frame: Change from baseline of global strain on echocardiogram at 1 year
Echocardiography will be used to measure myocardial characteristics such as global longitudinal strain
Change in Ejection fraction (EF)
Time Frame: Change from baseline in ejection fraction at 1-year
Cardiac Magnetic Resonance Imaging (cMRI) and echocardiography will be used to measure ventricular function
Change in Myocardial characteristics (Global strain on MRI)
Time Frame: Change from baseline of global strain on MRI at 1 year
Cardiac Magnetic Resonance Imaging (cMRI) will be used to measure myocardial characteristics
Change in functional exercise capacity of participants.
Time Frame: Change from baseline of exercise capacity at 1-year
Cardiopulmonary exercise stress testing (CPET) will be used to measure functional change in MVO2, RER, Exercise time, METs, and vitals.
Number of Participants Hospitalized for Cardiac Reasons or heart transplantation
Time Frame: Cardiac hospitalizations or transplantation at 1 year.
Hospitalization for cardiac reasons or heart transplantation
Number of Deaths
Time Frame: Number of deaths at 1 year
Number of patients who died during the study from all causes
Secondary Outcomes
- Change in functional Neuropsychological Testing(Change from baseline of neuropsychological testing at 1-year)
- Change Patient-Reported Outcomes Measurement Information System (PROMIS)(Change from baseline of PROMIS composite score at 1 year)
- Change in Neuro-QOL(Change from baseline of Neuro-QOL score at 1 year)
- Change in Kansas City Cardiomyopathy (KCCQ)(Change from baseline of KCCQ score at 1 year)
- Change in inflammatory serum biomarkers(Change from baseline of serum biomarkers at 1-year)
- Change in New York Heart Association (NYHA) Class(Change from baseline of NYHA Class at 1-year.)
Investigators
Anita Saraf
Assistant Professor
University of Pittsburgh