SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure

NCT06955260 | Not Yet Recruiting Phase 3

• 1 other identifier: 1245-0331
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 1

Brief Summary

Some people are born with a birth defect where they only have one functioning ventricle (lower chamber) in their heart. This condition can be initially managed with a Fontan operation, but there is a risk of developing Fontan Circulatory Failure (FCF) later in life. FCF occurs when the single working heart ventricle is no longer strong enough to pump blood throughout the body. This also means the heart has difficulty supplying oxygen to keep up with the needs of the body. As a result, individuals living with FCF may have some challenges carrying out day to day activities. A heart transplant is currently the only therapeutic option for individuals living with FCF. The investigators are conducting this trial to determine whether a medication called empagliflozin can help these people have a better quality of life.

Conditions

Congenital Heart Disease

Keywords

Fontan Circulatory Failure; Empagliflozin; Double-blind; randomized

Outcome Measures

Primary Outcomes (1)

• Hierarchical endpoint

  Primary hierarchical composite outcome will be analyzed using a win ratio based on the Finkelstein-Schoenfeld test. * All cause death (no. of participants) * Listing for heart transplantation or initiation of mechanical circulatory support (no. of participants) * Sustained ventricular tachycardia or aborted sudden cardiac death (no. of participants) * Hospital admission for management of FCF defined by any of the following: * Admission for intravenous diuretics (no. of participants) * Admission for intravenous inotropes (no. of participants) * Admission for ascites drainage (no. of participants) * Admission for management of new or worsening ascites of clinical significance (no. of participants) * Admission for management of arrhythmia (no. of participants) * Admission for management of lymphatic dysfunction (no. of participants) * ≥5 points change in the KCCQ-Clinical Summary Score (KCCQ-CSS) from baseline to Week 12 * Change in 6-minute walk distance f

  Week 12

Secondary Outcomes (8)

• All cause death

  Week 12

• Listing for heart transplantation or initiation of mechanical circulatory support

  Week 12

• Sustained ventricular tachycardia or aborted sudden cardiac death

  Week 12

• Hospital admission for management of FCF

  Week 12

• Change in KCCQ-Clinical Summary Score

  Week 12

Other Outcomes (19)

• Fontan revision surgery

  Week 12

• Fontan conversion surgery

  Week 12

• Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons

  Week 12

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Drug: Empagliflozin 10 mg

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Empagliflozin 10 mg DRUG

Participants will take 10 mg of empagliflozin once daily

Empagliflozin

Placebo OTHER

Participants will take 10 mg of placebo once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (≥18 years of age) with FCF, defined by dysfunction of the Fontan physiology that causes limitation to the individual's ability to carry out daily life activities, on standard of care therapy

You may not qualify if:

• Diuretic initiation or dose change ≤2 weeks prior to enrollment On a SGLT2 inhibitor currently or within 12-weeks prior to enrollment in the trial
• Allergic to or has a known intolerance to any of the ingredients in empagliflozin or other SGLT2 inhibitors
• Pregnant or planning a pregnancy during the duration of the trial or breast feeding
• Living with type 1 diabetes mellitus
• Has an unresolved acute illness (e.g., acute appendicitis, COVID-19, gastroenteritis)
• History of ketoacidosis
• Has an estimated glomerular filtration rate (eGFR) that is \<30 mL/min/1.73 m2 Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2-fold upper limit of normal (ULN) at screening
• Has a baseline systolic BP that is \<80 mmHg or ≥200 mmHg
• Planned hospital intervention during trial period for management of FCF defined as one of the following:
• Admission for intravenous diuretics
• Admission for intravenous inotropes
• Admission for ascites drainage
• Admission for new or worsening ascites of clinical significance
• Admission for management of arrhythmia
• Admission for management of lymphatic dysfunction

Sponsors & Collaborators

• Subodh Verma: lead
• Boehringer Ingelheim: collaborator
• Applied Health Research Centre: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery and Pharmacology & Toxicology

Model Details: Double-blind, randomized (1:1), placebo-controlled, parallel group trial of empagliflozin vs. placebo

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: May 2, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)