Clinical trial NCT06955260: SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
Official title: A Randomized Trial of SGLT2 Inhibition With Empagliflozin in Adults With Fontan Circulatory Failure (EMPA-HEART 3 CardioLink-12)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Congenital Heart Disease
Keywords: Fontan Circulatory Failure
Empagliflozin
Double-blind
randomized
Lead sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: Applied Health Research Centre
First posted: 2025-05-02
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized (1:1), placebo-controlled, parallel group trial of empagliflozin vs. placebo
Primary purpose: TREATMENT

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.

Detailed description: EMPA-HEART 3 CardioLink-12 is a global, multicentre, randomized, double-blinded, placebo-controlled, parallel group trial of empagliflozin vs. placebo in addition to standard of care therapy in adults with Fontan Circulatory Failure (FCF). A total of 410 individuals who provide written informed consent and meet the inclusion criteria following screening will be randomized (1:1) to receive either empagliflozin 10 mg once daily or matching placebo. During the 12-week follow-up, there will be four in-person and three telephone/virtual assessment visits.

The primary goal of this investigation is to determine whether 12 weeks of therapy with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, will improve clinical and participant-reported outcome measures in adults with FCF.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Admission for interventional cardiological or cardiac surgical procedure within 30-days prior to screening, or consideration for any cardiac surgical or interventional cardiological procedure during trial participation
* Admission for cardiac resynchronization therapy within 90-days prior to screening, or consideration of cardiac resynchronization therapy during trial participation
* Is unable to provide written informed consent, complete the trial or comply with the requirements of the trial protocol
* Participation in other interventional studies within 30-days of the screening visit that could influence any of the trial outcomes (exclusive of observational registries)
* Received intravenous diuretic within the previous 14-days
* On a heart transplant waiting list
* Current or imminent hospitalization for management of FCF

Primary outcomes:
measure: Hierarchical endpoint
timeFrame: Week 12
Secondary outcomes:
measure: All cause death
timeFrame: Week 12
measure: Listing for heart transplantation or initiation of mechanical circulatory support
timeFrame: Week 12
measure: Sustained ventricular tachycardia or aborted sudden cardiac death
timeFrame: Week 12
measure: Hospital admission for management of FCF
timeFrame: Week 12
measure: Change in KCCQ-Clinical Summary Score
timeFrame: Week 12
measure: Change in 6-minute walk test
timeFrame: Week 12
measure: Time to severe FCF
timeFrame: Week 12
measure: Change in FCF status
timeFrame: Week 12
Other outcomes:
measure: Fontan revision surgery
timeFrame: Week 12
measure: Fontan conversion surgery
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: Change in cardiopulmonary exercise testing (CPET) variables if collected for clinical reasons
timeFrame: Week 12
measure: NT-proBNP
timeFrame: Week 12
measure: Hemoglobin
timeFrame: Week 12
measure: Change in KCCQ score
timeFrame: Week 12
measure: Absolute change in KCCQ score
timeFrame: Week 12
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
References: