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

Overview

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

Interventions

• Drug Empagliflozin 10 MG
  Patient will be given 10 mg of Empagliflozin if randomized to the drug arm or will receive placebo drug for 1 year
• Drug Placebo
  To patients randomized to the placebo group, a placebo pill will be given

Primary outcome measures

• Change in Ejection fraction (EF) [Time frame: Change from baseline in ejection fraction at 1-year]
• Change in Myocardial characteristics (T1 mapping of cMRI) [Time frame: Change from baseline in T1 mapping at 1-year]
• Change in Myocardial characteristics (Global strain on MRI) [Time frame: Change from baseline of global strain on MRI at 1 year]
• Change in Myocardial characteristics (Global strain on echocardiogram) [Time frame: Change from baseline of global strain on echocardiogram at 1 year]
• Change in functional exercise capacity of participants. [Time frame: Change from baseline of exercise capacity at 1-year]
• Number of Participants Hospitalized for Cardiac Reasons or heart transplantation [Time frame: Cardiac hospitalizations or transplantation at 1 year.]
• Number of Deaths [Time frame: Number of deaths at 1 year]

Secondary outcome measures (6)

• Change in inflammatory serum biomarkers [Time frame: Change from baseline of serum biomarkers at 1-year]
• Change in functional Neuropsychological Testing [Time frame: Change from baseline of neuropsychological testing at 1-year]
• Change in New York Heart Association (NYHA) Class [Time frame: Change from baseline of NYHA Class at 1-year.]
• Change Patient-Reported Outcomes Measurement Information System (PROMIS) [Time frame: Change from baseline of PROMIS composite score at 1 year]
• Change in Kansas City Cardiomyopathy (KCCQ) [Time frame: Change from baseline of KCCQ score at 1 year]
• Change in Neuro-QOL [Time frame: Change from baseline of Neuro-QOL score at 1 year]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 3 centers

• Magee Women's Hospital — Pittsburgh
• Presbyterian Hospital — Pittsburgh
• Children's Hospital of Pittsburgh — Pittsburgh

Identifiers

NCT: NCT06260059 · STUDY23070148 · Pitt2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗