FontanPhase 4NCT07482943
The Effect of Dapagliflozin on Exercise and Cardiac Functional Status of Patients After Fontan Procedure
A Phase 4 study testing Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy in people with Fontan and Heart Failure, run by The University of Hong Kong at 2 sites in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Fontan, Heart Failure, Dapagliflozin
- What is being tested?
- Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesHong Kong
- Study dates
- 1 Jul 2026to Jul 2028
- Phase
- Phase 4
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with a functional single ventricle and who have undergone Fontan procedure
- Adolescents aged ≥ 12 years with body weight ≥30kg and adults
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong2 sites, 2 recruiting
- Recruiting
Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital
Hong Kong
Jacob Pak Lam Dr Ho, +852-35133888, jacobho@ha.org.hk
- Not yet recruiting
Queen Mary Hospital
Hong Kong
Ka Chun Timothy Dr Un, +852-22553111, mbbstimothy@gmail.com
Chun-Ka Dr Wong, Clinical Assistant Professor
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Fontan, Heart Failure, Dapagliflozin, Cardiovascular Diseases, Sodium-GLucose coTransporter-2 Inhibitors
- Being tested
- Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy
- Keywords
- fontan, heart failure, dapagliflozin, Sodium-glucose cotransporter 2 (SGLT2) inhibitor, Congenital heart disease
- Medical subject headings
- Heart Failure, Cardiovascular Diseases, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor TherapyDrug
Also called Dapagliflozin
Subjects in SGLT2 inhibitor Group will take dapagliflozin 5-10mg once daily orally from Visit 1 (Week 1) to Visit 3 (Week 12 ± 1)
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Other | Drug: SGLT2 inhibitor (Dapagliflozin 10mg)
12 week, Dapagliflozin 5-10mg once daily orally in Adolescents and Adults with Fontan Circulation Receives: Drug: Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal oxygen uptake (VO2 max) on cardiopulmonary exercise (CPX) at 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
Measured: At Visit 3 (3 months)
Secondary outcomes (12)
Metabolic equivalents (METs) on cardiopulmonary test (CPX)
Metabolic equivalents (METs) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
Measured: At Visit 3 (3 months)
Oxygen pulse on cardiopulmonary exercise (CPX) at 3 months
Oxygen pulse assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
Measured: At Visit 3 (3 months)
Anaerobic threshold (VO2 AT) on cardiopulmonary exercise (CPX) at 3 months
Anaerobic threshold (VO2 AT) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
Measured: At Visit 3 (3 months)
Ventilatory equivalent for oxygen (VE/VO2) on cardiopulmonary exercise (CPX) at 3 months
Ventilatory equivalent for oxygen (VE/VO2) on cardiopulmonary exercise (CPX) assessed during CPX for effect of of SGLT2 inhibitors in Fontan patients
Measured: At Visit 3 (3 months)
Cardiac biomarkers level
Cardiac biomarkers level, including NT-proBNP in Fontan patients at 3 months as assessed via blood tests for effect of SGLT2 inhibitors
Measured: At Visit 3 (3 months)
Systemic ventricular function
Effect of SGLT2 inhibitors on systemic ventricular function in Fontan patients as assessed by performing echocardiography at 3 months
Measured: At Visit 3 (3 months)
Systemic ventricle dimension
Effect of SGLT2 inhibitors on systemic ventricle dimension in Fontan patients as assessed by performing echocardiography at 3 months
Measured: At Visit 3 (3 months)
Atrioventricular valve regurgitation
Effect of SGLT2 inhibitors on atrioventricular valve regurgitation severity as assessed by echocardiography at 3 months
Measured: At Visit 3 (3 months)
Kansas City Cardiomyopathy Questionnaire (KCCQ) score
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.
Measured: At Visit 3 (3 months)
Paediatric Quality of Life (PedsQL)
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.
Measured: At Visit 3 (3 months)
Time to first occurrence of clinical events
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
Measured: At Visit 3 (3 months)
Occurrence of adverse events
Occurrence of adverse events in 3 months as assessed for safety and tolerability SGLT2 inhibitors in Fontan patients
Measured: At Visit 3 (3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start1 Jul 2026
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for FontanStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheung Yiu Fai, The University of Hong Kong
- Investigators
- Prof Yiu Fai Cheung, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07482943
- Sponsor's protocol ID
- DAPA01
- Status last verified
- Jul 2026
- First submitted
- 10 Mar 2026
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fernandes SM, McElhinney DB, Khairy P, Graham DA, Landzberg MJ, Rhodes J. Serial cardiopulmonary exercise testing in patients with previous Fontan surgery. Pediatr Cardiol. 2010 Feb;31(2):175-80. doi: 10.1007/s00246-009-9580-5.
PubMed 19915891Nunez J, Palau P, Dominguez E, Mollar A, Nunez E, Ramon JM, Minana G, Santas E, Facila L, Gorriz JL, Sanchis J, Bayes-Genis A. Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study. Clin Cardiol. 2018 Apr;41(4):476-480. doi: 10.1002/clc.22899. Epub 2018 Apr 17.
PubMed 29663436Chen K, Nie Z, Shi R, Yu D, Wang Q, Shao F, Wu G, Wu Z, Chen T, Li C. Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure. JAMA Netw Open. 2023 Aug 1;6(8):e2330754. doi: 10.1001/jamanetworkopen.2023.30754.
PubMed 37615988McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.
PubMed 31535829Pascual ES, Zurita MB, Sebastian JD, Silva LG, Peinado AA, Aguado FG. Comparison of Myocardial Deformation by Speckle-Tracking Echocardiography and Cardiac Magnetic Resonance in Patients with Fontan Circulation: Diagnostic Algorithm. J Cardiovasc Echogr. 2021 Jul-Sep;31(3):144-150. doi: 10.4103/jcecho.jcecho_126_20. Epub 2021 Oct 26.
PubMed 34900549Grattan M, Mertens L, Grosse-Wortmann L, Friedberg MK, Cifra B, Dragulescu A. Ventricular Torsion in Young Patients With Single-Ventricle Anatomy. J Am Soc Echocardiogr. 2018 Dec;31(12):1288-1296. doi: 10.1016/j.echo.2018.07.018. Epub 2018 Oct 17.
PubMed 30340887Bellsham-Revell HR, Tibby SM, Bell AJ, Miller OI, Razavi R, Greil GF, Simpson JM. Tissue Doppler time intervals and derived indices in hypoplastic left heart syndrome. Eur Heart J Cardiovasc Imaging. 2012 May;13(5):400-7. doi: 10.1093/ejechocard/jer271. Epub 2011 Dec 8.
PubMed 22157969Cordina R, Ministeri M, Babu-Narayan SV, Ladouceur M, Celermajer DS, Gatzoulis MA, Uebing A, Li W. Evaluation of the relationship between ventricular end-diastolic pressure and echocardiographic measures of diastolic function in adults with a Fontan circulation. Int J Cardiol. 2018 May 15;259:71-75. doi: 10.1016/j.ijcard.2018.02.045. Epub 2018 Feb 12.
PubMed 29472024Friedberg MK, Silverman NH. The systolic to diastolic duration ratio in children with hypoplastic left heart syndrome: a novel Doppler index of right ventricular function. J Am Soc Echocardiogr. 2007 Jun;20(6):749-55. doi: 10.1016/j.echo.2006.11.014.
PubMed 17543747Newland DM, Law YM, Albers EL, Friedland-Little JM, Ahmed H, Kemna MS, Hong BJ. Early Clinical Experience with Dapagliflozin in Children with Heart Failure. Pediatr Cardiol. 2023 Jan;44(1):146-152. doi: 10.1007/s00246-022-02983-0. Epub 2022 Aug 10.
PubMed 35948644Lopaschuk GD, Verma S. Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: A State-of-the-Art Review. JACC Basic Transl Sci. 2020 Jun 22;5(6):632-644. doi: 10.1016/j.jacbts.2020.02.004. eCollection 2020 Jun.
PubMed 32613148Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1.
PubMed 35379503Poh C, Hornung T, Celermajer DS, Radford DJ, Justo RN, Andrews D, du Plessis K, Iyengar AJ, Winlaw D, d'Udekem Y. Modes of late mortality in patients with a Fontan circulation. Heart. 2020 Sep;106(18):1427-1431. doi: 10.1136/heartjnl-2019-315862. Epub 2020 Feb 25.
PubMed 32098807Dennis M, Zannino D, du Plessis K, Bullock A, Disney PJS, Radford DJ, Hornung T, Grigg L, Cordina R, d'Udekem Y, Celermajer DS. Clinical Outcomes in Adolescents and Adults After the Fontan Procedure. J Am Coll Cardiol. 2018 Mar 6;71(9):1009-1017. doi: 10.1016/j.jacc.2017.12.054.
PubMed 29495980Skorek P, Fraczek-Jucha MM, Sarnecka A, Skubera M, Libiszewska N, Tomkiewicz-Pajak L. Experience with sodium glucose cotransporter-2 inhibitors in adult patients with Fontan circulation. Adv Clin Exp Med. 2025 Sep;34(9):1493-1499. doi: 10.17219/acem/194617.
PubMed 39807605
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dapagliflozin on Exercise and Cardiac Functional Status of Patients After Fontan Procedure
- ClinicalTrials.gov ID
- NCT07482943
- Acronym / sponsor ID
- DAPA01
- Conditions
- Fontan, Heart Failure, Dapagliflozin, Cardiovascular Diseases, Sodium-GLucose coTransporter-2 Inhibitors
- Keywords
- fontan, heart failure, dapagliflozin, Sodium-glucose cotransporter 2 (SGLT2) inhibitor, Congenital heart disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jul 2026 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 19 Mar 2026 (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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Other | Drug: Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor TherapyDrug: SGLT2 inhibitor (Dapagliflozin 10mg) 12 week, Dapagliflozin 5-10mg once daily orally in Adolescents and Adults with Fontan Circulation |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with a functional single ventricle and who have undergone Fontan procedure
- Adolescents aged ≥ 12 years with body weight ≥30kg and adults
Key exclusion criteria (16 listed)
- 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
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 |
|---|---|---|
| Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor TherapyAlso: DapagliflozinSubjects in SGLT2 inhibitor Group will take dapagliflozin 5-10mg once daily orally from Visit 1 (Week 1) to Visit 3 (Week 12 ± 1) | Drug | Dapagliflozin |
Primary outcome
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
12 secondary outcomes
Metabolic equivalents (METs) on cardiopulmonary test (CPX)
Time frame: At Visit 3 (3 months)
Oxygen pulse on cardiopulmonary exercise (CPX) at 3 months
Time frame: At Visit 3 (3 months)
Anaerobic threshold (VO2 AT) on cardiopulmonary exercise (CPX) at 3 months
Time frame: 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)
Cardiac biomarkers level
Time frame: At Visit 3 (3 months)
Systemic ventricular function
Time frame: At Visit 3 (3 months)
Systemic ventricle dimension
Time frame: At Visit 3 (3 months)
Atrioventricular valve regurgitation
Time frame: At Visit 3 (3 months)
Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Time frame: At Visit 3 (3 months)
Paediatric Quality of Life (PedsQL)
Time frame: At Visit 3 (3 months)
Time to first occurrence of clinical events
Time frame: At Visit 3 (3 months)
Occurrence of adverse events
Time frame: At Visit 3 (3 months)
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 28 Jul 2026.
- Background: PubMed 19915891Fernandes SM, McElhinney DB, Khairy P, Graham DA, Landzberg MJ, Rhodes J. Serial cardiopulmonary exercise testing in patients with previous Fontan surgery. Pediatr Cardiol. 2010 Feb;31(2):175-80. doi: 10.1007/s00246-009-9580-5.
- Background: PubMed 29663436Nunez J, Palau P, Dominguez E, Mollar A, Nunez E, Ramon JM, Minana G, Santas E, Facila L, Gorriz JL, Sanchis J, Bayes-Genis A. Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study. Clin Cardiol. 2018 Apr;41(4):476-480. doi: 10.1002/clc.22899. Epub 2018 Apr 17.
- Background: PubMed 37615988Chen K, Nie Z, Shi R, Yu D, Wang Q, Shao F, Wu G, Wu Z, Chen T, Li C. Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure. JAMA Netw Open. 2023 Aug 1;6(8):e2330754. doi: 10.1001/jamanetworkopen.2023.30754.
- Background: PubMed 31535829McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.
- Background: PubMed 34900549Pascual ES, Zurita MB, Sebastian JD, Silva LG, Peinado AA, Aguado FG. Comparison of Myocardial Deformation by Speckle-Tracking Echocardiography and Cardiac Magnetic Resonance in Patients with Fontan Circulation: Diagnostic Algorithm. J Cardiovasc Echogr. 2021 Jul-Sep;31(3):144-150. doi: 10.4103/jcecho.jcecho_126_20. Epub 2021 Oct 26.
- Background: PubMed 30340887Grattan M, Mertens L, Grosse-Wortmann L, Friedberg MK, Cifra B, Dragulescu A. Ventricular Torsion in Young Patients With Single-Ventricle Anatomy. J Am Soc Echocardiogr. 2018 Dec;31(12):1288-1296. doi: 10.1016/j.echo.2018.07.018. Epub 2018 Oct 17.
- Background: PubMed 22157969Bellsham-Revell HR, Tibby SM, Bell AJ, Miller OI, Razavi R, Greil GF, Simpson JM. Tissue Doppler time intervals and derived indices in hypoplastic left heart syndrome. Eur Heart J Cardiovasc Imaging. 2012 May;13(5):400-7. doi: 10.1093/ejechocard/jer271. Epub 2011 Dec 8.
- Background: PubMed 29472024Cordina R, Ministeri M, Babu-Narayan SV, Ladouceur M, Celermajer DS, Gatzoulis MA, Uebing A, Li W. Evaluation of the relationship between ventricular end-diastolic pressure and echocardiographic measures of diastolic function in adults with a Fontan circulation. Int J Cardiol. 2018 May 15;259:71-75. doi: 10.1016/j.ijcard.2018.02.045. Epub 2018 Feb 12.
- Background: PubMed 17543747Friedberg MK, Silverman NH. The systolic to diastolic duration ratio in children with hypoplastic left heart syndrome: a novel Doppler index of right ventricular function. J Am Soc Echocardiogr. 2007 Jun;20(6):749-55. doi: 10.1016/j.echo.2006.11.014.
- Background: PubMed 35948644Newland DM, Law YM, Albers EL, Friedland-Little JM, Ahmed H, Kemna MS, Hong BJ. Early Clinical Experience with Dapagliflozin in Children with Heart Failure. Pediatr Cardiol. 2023 Jan;44(1):146-152. doi: 10.1007/s00246-022-02983-0. Epub 2022 Aug 10.
- Background: PubMed 32613148Lopaschuk GD, Verma S. Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: A State-of-the-Art Review. JACC Basic Transl Sci. 2020 Jun 22;5(6):632-644. doi: 10.1016/j.jacbts.2020.02.004. eCollection 2020 Jun.
- Background: PubMed 35379503Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1.
- 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.
Prof Yiu Fai Cheung principal investigator
The University of Hong Kong
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy in people with Fontan and Heart Failure, run by The University of Hong Kong at 2 sites in Hong Kong.
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 2 inclusion and 16 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 28 Jul 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 Hong Kong. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Prof Yiu Fai Cheung (+852-35133888, xfcheung@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal oxygen uptake (VO2 max) on cardiopulmonary exercise (CPX) at 3 months (time frame: At Visit 3 (3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07482943, which also lists 23 linked publications.
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 28 Jul 2026.