Clinical trial NCT06762964: CAMEO-FONTAN -Dapagliflozin in the Failing Fontan Circulation
Official title: Cardiac and Metabolic Effects of Dapagliflozin in the Failing Fontan Circulation: A Phase II, Prospective, Double-Blind Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Fontan Circulation
Single Ventricle Heart Disease
HFpEF - Heart Failure With Preserved Ejection Fraction
Keywords: Fontan
HFpEF
SGLT2 inhibitors
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2025-01-08
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 6 months affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in adults with failing Fontan circulation.


Eligibility criteria: Inclusion Criteria

Subjects are eligible to be randomized in the study only if all the following inclusion criteria and none of the exclusion criteria apply:

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-III) with no non-cardiac or ischemia explanation
6. Undergoing clinically indicated cardiac catheterization
7. Elevated pulmonary capillary wedge pressure (PCWP) during exercise (≥25 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

Primary outcomes:
measure: Pulmonary capillary wedge pressure (PCWP) at rest
timeFrame: Baseline, 24 Months
measure: Pulmonary capillary wedge pressure with feet elevated
timeFrame: Baseline, 24 Months
measure: Pulmonary capillary wedge pressure at 20W exercise
timeFrame: Baseline, 24 Months
Secondary outcomes:
measure: Right atrial pressure at rest
timeFrame: Baseline, 24 Months
measure: Right atrial pressure with exercise
timeFrame: Baseline, 24 Months
measure: Pulmonary artery pressures at rest
timeFrame: Baseline, 24 Months
measure: Pulmonary artery pressures with exercise
timeFrame: Baseline, 24 Months
measure: Cardiac output at rest
timeFrame: Baseline, 24 Months
measure: Cardiac output with exercise
timeFrame: Baseline, 24 Months
measure: Peak oxygen consumption (VO2) during exercise
timeFrame: Baseline, 24 Months
measure: Change in plasma volume
timeFrame: Baseline, 24 Months
measure: Change in blood volume
timeFrame: Baseline, 24 Months
measure: SF-36 quality of life (QOL)
timeFrame: Baseline, 24 Months
measure: Change in fat mass
timeFrame: Baseline, 24 Months
measure: Change in fat free mass
timeFrame: Baseline, 24 Months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Luke Burchill, M.B.B.S., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: