Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial

Sponsor
The University of Hong Kong
Study ID
NCT06668389
Phase
PHASE4
Status
Recruiting
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Conditions

  • Congenital Heart Disease
  • Dapagliflozin (Forxiga)
  • Pulmonary Regurgitation
  • Repaired Tetralogy of Fallot (rTOF)
  • Sodium-glucose Cotransporter 2 (SGLT2) Inhibitor

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

Repaired Tetralogy of Fallot (rTOF) is the leading cause of congenital cyanotic heart disease worldwide, involving up to 7-10% of congenital heart disease. With advances in open-heart surgical repair techniques and medical therapies, there is a significant increase in patients with rTOF surviving till late adulthood. One sequalae that nearly all rTOF patients develop during their lifetime is significant pulmonary regurgitation. Pulmonary regurgitation causes progressive right ventricular dilatation and systolic dysfunction, which in turn impairs cardio-pulmonary function and overall survival. There is currently no pharmacological therapy proven to improve cardio-pulmonary function in rTOF patients. In a double-blind, placebo controlled, randomized controlled trial involving 33 rTOF patients, the use of beta-adrenergic receptor blocker Bisoprolol failed to improve maximal oxygen uptake (VO2 max) in the treatment group. Furthermore, there was no significant change in dimension of right ventricle on cardiac imaging, or heart failure biomarkers including brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). In the APPROPRIATE trial involving 64 patients, angiotensin-converting-enzyme inhibitor (ACEI) Ramipril similarly failed to improve VO2 max despite an improved right ventricular long-axis shortening. In REDEFINE trial, 95 rTOF patients were randomized in to receive angiotensin receptor blocker (ARB) Losartan and control. At the end of study, there was no significant difference between the two groups in VO2 max, right ventricular ejection fraction, and other key outcomes. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a promising therapy for rTOF patients. Clinical trials consistently demonstrated that SGLT2 inhibitors reduce heart failure hospitalization and mortality among patients with heart failure with or without diabetes mellitus. There have been growing body of evidence that demonstrate that SGLT2 inhibitors improve right ventricular function. In a preclinical study of rat with pulmonary hypertension induced right ventricular failure, empagliflozin was found to reduce pulmonary pressure, alleviate right ventricular hypertrophy and reduce myocardial fibrosis. In a pilot study involving 10 patients with adult congenital heart disease and systemic right ventricular failure, SGLT2 inhibitors improved cardio-pulmonary function as reflected by 6-minute walk test performance and New York Heart Association functional status. Most recently, investigators from DAPA-SERVE randomized controlled trial reported that among 92 patients with systemic right ventricular failure, those randomized to receive SGLT2 inhibitors had superior systemic right ventricular function with larger fractional area change (FAC) and more negative free-wall global longitudinal strain. Nevertheless, as these trials involve patients with right ventricular connections to the systemic circulation rather than pulmonary circulation in rTOF, it is uncertain whether the trial results can be extrapolated to the rTOF population. The critical knowledge gap our proposed randomized controlled trial seeks to address is whether SGLT2 inhibitors improve cardio-pulmonary function in rTOF patients.

Key Dates

Start date
May 12, 2025
Status verified
May 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
106 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: SGLT2 inhibitor Group
    Dapagliflozin 10mg once daily orally from Visit 1 (Week 1) to Visit 3 (Week 12 ± 1)
  • No Intervention: Control Group
    Routine care

Primary Outcome Measure

Maximal oxygen uptake (VO2 max) on cardiopulmonary exercise (CPX) at 3 months [ Time Frame: At Visit 3 (3 months) ]

Central Contacts

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