Congenital Heart DiseasePhase 3EMPA-HEART-3NCT06955260
SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
A Phase 3 study testing Empagliflozin 10 mg in people with Congenital Heart Disease, run by Subodh Verma at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Empagliflozin 10 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 410 participants
- Where
- 2 sitesCanada
- Study dates
- 29 May 2026to Mar 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
University Health Network
Toronto, Ontario, M5G 2C4
S. Lucy Roche, MD, 416-340-5502, lucy.roche@uhn.ca
S. Lucy Roche, MD
- Recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Jasmine Grewal, MD, 604-806-8804, jagrewal@providencehealth.bc.ca
About this study
Official title: A Randomized Trial of SGLT2 Inhibition With Empagliflozin in Adults With Fontan Circulatory Failure (EMPA-HEART 3 CardioLink-12)
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.
Read the 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.
- Conditions
- Congenital Heart Disease
- Being tested
- Empagliflozin 10 mg, Placebo
- Keywords
- Fontan Circulatory Failure, Empagliflozin, Double-blind, randomized
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 mgDrug
Participants will take 10 mg of empagliflozin once daily
PlaceboOther
Participants will take 10 mg of placebo once daily
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Active comparator | Not described Receives: Drug: Empagliflozin 10 mg |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 12
Secondary outcomes (8)
All cause death
All cause death (no. of participants)
Measured: Week 12
Listing for heart transplantation or initiation of mechanical circulatory support
Listing for heart transplantation or initiation of mechanical circulatory support (no. of participants)
Measured: Week 12
Sustained ventricular tachycardia or aborted sudden cardiac death
Sustained ventricular tachycardia or aborted sudden cardiac death (no. of participants)
Measured: Week 12
Hospital admission for management of FCF
Hospital admission for management of FCF (in number of participants) as 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)
Measured: Week 12
Change in KCCQ-Clinical Summary Score
≥5 points change in the KCCQ-Clinical Summary Score (KCCQ-CSS) from baseline (no. of participants)
Measured: Week 12
Change in 6-minute walk test
Change in 6-minute walk distance (in meters)
Measured: Week 12
Time to severe FCF
Time to severe FCF, defined as the first occurrence of any of the following:
- Death (days)
- Placement on heart or combined heart and liver transplantation list (days)
- Initiation of palliative care because the individual is not a heart transplant candidate (days)
- Fontan take down surgery (days)
Measured: Week 12
Change in FCF status
Investigator-reported global change in FCF status (days)
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2025
- Study start29 May 2026
- Primary completionDec 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomized (1:1), placebo-controlled, parallel group trial of empagliflozin vs. placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Subodh Verma
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Applied Health Research Centre
- Responsible party
- Sponsor-investigator, Subodh Verma, Canadian Medical and Surgical Knowledge Translation Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06955260
- Sponsor's protocol ID
- 1245-0331
- Acronym
- EMPA-HEART-3
- Status last verified
- Aug 2026
- First submitted
- 15 Mar 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of SGLT2 Inhibition With Empagliflozin in Adults With Fontan Circulatory Failure (EMPA-HEART 3 CardioLink-12)
- ClinicalTrials.gov ID
- NCT06955260
- Acronym / sponsor ID
- EMPA-HEART-3 / 1245-0331
- Conditions
- Congenital Heart Disease
- Keywords
- Fontan Circulatory Failure, Empagliflozin, Double-blind, randomized
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Subodh VermaUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Applied Health Research Centre
- Study start
- 29 May 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 2 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomized (1:1), placebo-controlled, parallel group trial of empagliflozin vs. placebo
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Active comparator | Drug: Empagliflozin 10 mg |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (22 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 10 mgParticipants will take 10 mg of empagliflozin once daily | Drug | Empagliflozin |
| PlaceboParticipants will take 10 mg of placebo once daily | Other | Placebo |
Primary outcome
Hierarchical endpoint
Time frame: Week 12
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
8 secondary outcomes
All cause death
Time frame: Week 12
Listing for heart transplantation or initiation of mechanical circulatory support
Time frame: Week 12
Sustained ventricular tachycardia or aborted sudden cardiac death
Time frame: Week 12
Hospital admission for management of FCF
Time frame: Week 12
Change in KCCQ-Clinical Summary Score
Time frame: Week 12
Change in 6-minute walk test
Time frame: Week 12
Time to severe FCF
Time frame: Week 12
Change in FCF status
Time frame: Week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Empagliflozin 10 mg in people with Congenital Heart Disease, run by Subodh Verma at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicole Cooke, CCRP (416-864-6060 ext. 7835, Nicole.cooke@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hierarchical endpoint (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.