The Effect of Dapagliflozin on Exercise and Cardiac Functional Status of Patients After Fontan Procedure

March 15, 2026 updated by: Cheung Yiu Fai, The University of Hong Kong

While the Fontan operation improves survival for patients with a functional single ventricle, complications like heart failure remain prevalent during follow-up, causing frequent hospitalizations and reduced quality of life. Currently, there are no evidence-based heart failure therapies or guidelines for patients with Fontan palliation. There is growing interest in using sodium-glucose cotransporter 2 inhibitors (SGLT2i) to optimize cardiac conditions in this group. SGLT2i's observed benefits relate to protective effects on cardiac energy metabolism, renal function, sympathetic activation, inflammation, oxidative stress, erythropoiesis, and vascular function. Therefore, SGLT2i may represent a new therapeutic agent to improve exercise capacity and ventricular function in patients with Fontan circulation.

This prospective, open-label, single-arm clinical trial investigates the FDA-approved drug dapagliflozin. An open-label design is utilized due to the relatively small cohort of patients with complex underlying hearts. The trial will be conducted at Hong Kong Children's Hospital (the sole pediatric cardiology center in Hong Kong) and Queen Mary Hospital (the largest tertiary referral center for adult congenital heart patients). The total study duration is 2 years.

Subjects will participate for 3 months, receiving oral dapagliflozin 10mg once daily. The primary endpoint is VO2 max (maximum rate of oxygen consumption) during cardiopulmonary exercise testing at 3 months. Secondary assessments include questionnaires, history taking, physical examinations, 12-lead electrocardiogram, blood tests, echocardiography, bioelectrical impedance analysis, and urine pregnancy tests.

If the hypothesis holds true, clinical translation of this project will: i) Improve long-term outcomes and quality-of-life for Fontan patients, reducing the healthcare burden from repeated heart failure hospitalizations; ii) Revolutionize the management of Fontan-associated heart failure by introducing SGLT2i as a novel, evidence-based therapy locally and globally; iii) Pave the way for multicenter international trials evaluating SGLT2i in the Fontan population and broader congenital heart diseases.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Eligible patients with Fontan circulation who meet all predefined inclusion and exclusion criteria will be recruited from Queen Mary Hospital and Hong Kong Children's Hospital in Hong Kong. Prospective candidates will undergo a screening interview conducted by the research staff. During this interview, the objectives of the clinical trial, the required procedures, and any potential risks will be comprehensively explained. Prior to formal enrollment and the initiation of any study-specific procedures, written informed consent will be legally obtained from the patient or their designated legal guardian.

The study protocol involves a series of scheduled clinical assessments, beginning with a baseline evaluation at Visit 1. During this initial visit, patients will undergo a comprehensive medical history review and a physical examination. Baseline vital signs, including blood pressure, pulse rate, and resting oxygen saturation via pulse oximetry, will be recorded. Routine cardiovascular evaluations will include standard 12-lead electrocardiography. Unless performed within the preceding three months, a comprehensive laboratory panel will be drawn; this includes a complete blood count, renal and liver function tests, calcium and phosphate levels, N-terminal pro b-type natriuretic peptide (NT-proBNP), hemoglobin A1c, fasting glucose, and a lipid profile. Additionally, a urine pregnancy test will be administered to all women of childbearing potential. To establish baseline patient-reported outcomes, participants will complete either the Kansas City Cardiomyopathy Questionnaire (KCCQ) or the Paediatric Quality of Life Inventory (PedsQL).

Specialized cardiovascular diagnostics and subsequent follow-up evaluations will be conducted at Visit 1 (Week 4 ± 1) and Visit 3 (Week 12 ± 1). At the Week 12 follow-up visit, patients will complete a re-administration of the KCCQ or PedsQL questionnaires. During both specified visits, patients will undergo cardiopulmonary exercise testing (CPX) under the direct supervision of a cardiologist. This testing is designed to evaluate critical functional parameters, including peak oxygen consumption (VO₂), total functional capacity measured in metabolic equivalents (METs), oxygen pulse as a surrogate for stroke volume, the anaerobic threshold (VO₂ AT), and ventilatory efficiency (VE/VO₂).

In conjunction with the exercise testing, comprehensive echocardiography will be performed by an independent echocardiographer at Visit 1 and Visit 3, though the baseline scan may be waived if a comprehensive assessment is available from the preceding three years. The echocardiographic analysis will utilize color Doppler flow imaging for the semi-quantitative assessment of systemic atrioventricular (AV) valve regurgitation severity. Conventional pulsed-wave Doppler will be employed to measure early and late diastolic AV valve inflow velocities, allowing for the calculation of the AV systolic-to-diastolic ratio based on the regurgitant jet, which serves as a clinical correlate for ventricular end-diastolic pressure. Furthermore, pulsed-wave tissue Doppler imaging (TDI) will be conducted in the apical four-chamber view. By positioning the sample volume at the lateral AV annulus, researchers will record systolic, early diastolic, and late diastolic velocities to calculate the TDI-based myocardial performance index (MPI). Finally, speckle-tracking echocardiography (STE) will be applied to accurately quantify the systolic and diastolic myocardial deformation, or strain, of the single ventricle.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Prof Yiu Fai Cheung
  • Phone Number: +852-35133888
  • Email: xfcheung@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
        • Contact:
          • Chun-Ka Dr Wong, Clinical Assistant Professor
        • Contact:
      • Hong Kong, Hong Kong
        • Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a functional single ventricle and who have undergone Fontan procedure
  • Adolescents aged ≥ 12 years with body weight ≥30kg and adults

Exclusion Criteria:

  • Planned cardiac and/or non-cardiac surgery in 3 months
  • Arrhythmias requiring change in therapy in recent 6 months
  • Intervention procedure within 6 months prior to enrollment
  • Documented structural abnormalities of the Fontan circulation
  • Chronic kidney disease stages 4 to 5
  • Inability to perform cardiopulmonary test
  • Recent use of SGLT2 inhibitors within 6 months
  • Known hypersensitivity to SGLT2 inhibitors
  • History of diabetic ketoacidosis
  • Recent symptomatic hypoglycaemia within 6 months
  • Insulin dependent diabetes mellitus
  • History of perineum infection
  • Recent urinary tract infection within 6 months
  • Recent genital infection within 6 months
  • Other known contraindications to SGLT2 inhibitor
  • Pregnancy or breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Dapagliflozin

Drug: SGLT2 inhibitor (Dapagliflozin 10mg)

12 week, Dapagliflozin 5-10mg once daily orally in Adolescents and Adults with Fontan Circulation
Drug: Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy
Subjects in SGLT2 inhibitor Group will take dapagliflozin 5-10mg once daily orally from Visit 1 (Week 1) to Visit 3 (Week 12 ± 1)
Other Names:
  • Dapagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal oxygen uptake (VO2 max) on cardiopulmonary exercise (CPX) at 3 months
Time Frame: At Visit 3 (3 months)
Efficacy of SGLT2 inhibitors for improving cardiopulmonary function as assessed the maximal oxygen uptake (VO2 max) on cardiopulmonary exercise testing in Fontan patients at 3 months
At Visit 3 (3 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metabolic equivalents (METs) on cardiopulmonary test (CPX)
Time Frame: At Visit 3 (3 months)
Metabolic equivalents (METs) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)
Oxygen pulse on cardiopulmonary exercise (CPX) at 3 months
Time Frame: At Visit 3 (3 months)
Oxygen pulse assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)
Anaerobic threshold (VO2 AT) on cardiopulmonary exercise (CPX) at 3 months
Time Frame: At Visit 3 (3 months)
Anaerobic threshold (VO2 AT) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)
Ventilatory equivalent for oxygen (VE/VO2) on cardiopulmonary exercise (CPX) at 3 months
Time Frame: At Visit 3 (3 months)
Ventilatory equivalent for oxygen (VE/VO2) on cardiopulmonary exercise (CPX) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)
Cardiac biomarkers level
Time Frame: At Visit 3 (3 months)
Cardiac biomarkers level, including NT-proBNP in Fontan patients at 3 months as assessed via blood tests for effect of SGLT2 inhibitors
At Visit 3 (3 months)
Systemic ventricular function
Time Frame: At Visit 3 (3 months)
Effect of SGLT2 inhibitors on systemic ventricular function in Fontan patients as assessed by performing echocardiography at 3 months
At Visit 3 (3 months)
Systemic ventricle dimension
Time Frame: At Visit 3 (3 months)
Effect of SGLT2 inhibitors on systemic ventricle dimension in Fontan patients as assessed by performing echocardiography at 3 months
At Visit 3 (3 months)
Atrioventricular valve regurgitation
Time Frame: At Visit 3 (3 months)
Effect of SGLT2 inhibitors on atrioventricular valve regurgitation severity as assessed by echocardiography at 3 months
At Visit 3 (3 months)
Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Time Frame: At Visit 3 (3 months)
Kansa City Cardiomyopathy Questionnaire (KCCQ) score as completed with Fontan patients for effect of SGLT2 inhibitors. The KCCQ Overall Summary Score ranges from a minimum of 0 to a maximum of 100. Higher scores indicate a better outcome, reflecting fewer symptoms, less physical limitation, and better quality of life.
At Visit 3 (3 months)
Paediatric Quality of Life (PedsQL)
Time Frame: At Visit 3 (3 months)
Paediatric Quality of Life (PedsQL) as completed with Fontan patients for effect of SGLT2 inhibitors. The Total Scale Score is transformed to a scale ranging from a minimum of 0 to a maximum of 100. Higher scores mean a better outcome, indicating fewer problems and better health-related quality of life.
At Visit 3 (3 months)
Time to first occurrence of clinical events
Time Frame: At Visit 3 (3 months)
Time to first occurrence of clinical events, including heart failure hospitalization, incident arrhythmia, and cardiovascular mortality in 3 months safety as assessed for tolerability of SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)
Occurrence of adverse events
Time Frame: At Visit 3 (3 months)
Occurrence of adverse events in 3 months as assessed for safety and tolerability SGLT2 inhibitors in Fontan patients
At Visit 3 (3 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Prof Yiu Fai Cheung, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

March 10, 2026

First Submitted That Met QC Criteria

March 15, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 15, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAPA01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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