CAMEO-FONTAN -Dapagliflozin in the Failing Fontan Circulation

Cardiac and Metabolic Effects of Dapagliflozin in the Failing Fontan Circulation: A Phase II, Prospective, Double-Blind Study

The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 3 months affects peripheral venous pressure at rest and during exercise in adults with failing Fontan circulation.

Inclusion Criteria

1. Signed informed consent prior to any study specific procedures
2. History of Fontan procedure
3. Male or female subject
4. Age ≥ 18
5. Symptoms of dyspnea (NYHA II-IV) with no non-cardiac or ischemia explanation
6. Elevated peripheral venous pressure (PVP) at rest or during exercise (≥20 mmHg) ascertained at Visit 1. Patients that have consented to study procedures but do not meet this invasive criterion will be considered as screen failures and will not be randomized.

Exclusion Criteria

1. Type I diabetes
2. Any of the following medications: Insulin or Pramlintide, Sandostatin, Akeega (abiraterone acetate), Growth Hormone (Somatogrogon-GHLA), Lithium, Chloroquine, Hydroxychloroquine, Thioctic acid (alpha lipoic acid), Empagliflozin or Canagliflozin
3. Recent hospitalization (<30 days) or revascularization (<90 days)
4. Significant valvular heart disease (≥moderate stenosis, >moderate regurgitation)
5. Significant Fontan obstruction with resting SVC-IVC gradient >4 mmHg
6. Primary cardiomyopathy (such as amyloid)
7. Dyspnea due to primary lung disease or myocardial ischemia in the opinion of the investigator
8. Severe anemia (hemoglobin <9 gm/dl)
9. Severe kidney disease (estimated GFR<30) or liver disease
10. Women of childbearing potential not willing to use a medically accepted method of contraception OR who are currently pregnant (confirmed with positive pregnancy test) or breast feeding.
11. History of serious hypersensitivity reaction to dapagliflozin
12. Subjects on dialysis
13. Subjects with severe liver disease with history of decompensation including ascites or encephalopathy or variceal bleeding
14. Single ventricle heart disease without Fontan palliation
15. Those with a history of Fontan takedown