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

NCT07482943 | Recruiting Phase 4 FDA Drug

• 1 other identifier: DAPA01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Fontan; Heart Failure; Dapagliflozin; Sodium-GLucose coTransporter-2 Inhibitors; Cardiovascular Diseases

Keywords

fontan; heart failure; dapagliflozin; Sodium-glucose cotransporter 2 (SGLT2) inhibitor; Congenital heart disease

Outcome Measures

Primary Outcomes (1)

• 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

  At Visit 3 (3 months)

Secondary Outcomes (12)

• Metabolic equivalents (METs) on cardiopulmonary test (CPX)

  At Visit 3 (3 months)

• Oxygen pulse on cardiopulmonary exercise (CPX) at 3 months

  At Visit 3 (3 months)

• Anaerobic threshold (VO2 AT) on cardiopulmonary exercise (CPX) at 3 months

  At Visit 3 (3 months)

• Ventilatory equivalent for oxygen (VE/VO2) on cardiopulmonary exercise (CPX) at 3 months

  At Visit 3 (3 months)

• Cardiac biomarkers level

  At Visit 3 (3 months)

Study Arms (1)

Dapagliflozin

OTHER

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

Interventions

Dapagliflozin (5-10 mg daily) - SGLT2 Inhibitor Therapy DRUG

Subjects in SGLT2 inhibitor Group will take dapagliflozin 5-10mg once daily orally from Visit 1 (Week 1) to Visit 3 (Week 12 ± 1)

Also known as: Dapagliflozin

Dapagliflozin

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (2)

Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital

Hong Kong, Hong Kong

RECRUITING

Queen Mary Hospital

Hong Kong, Hong Kong

NOT YET RECRUITING

Related Publications (23)

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MeSH Terms

Conditions

Heart Failure; Cardiovascular Diseases; Heart Defects, Congenital

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Prof Yiu Fai Cheung

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof Yiu Fai Cheung

CONTACT

+852-35133888; xfcheung@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 19, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (2)