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.

Study Overview

• Status: Recruiting
• Conditions: Single Ventricle Heart Disease; Fontan Circulation; HFpEF - Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Dapagliflozin tablet; Drug: Placebo Tablet

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amanda Wozniak; Phone Number: 507-266-1976; Email: Wozniak.Amanda@mayo.edu
• Study Contact Backup: Name: Yusef Maarouf; Phone Number: 507-422-5755; Email: Maarouf.Yusef@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Luke Burchill, M.B.B.S., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Tablet; Patient will take 10mg placebo tablet once daily for 12 weeks
Experimental: Dapagliflozin	Drug: Dapagliflozin tablet; Patient will take a 10mg tablet of Dapagliflozin once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral venous pressure (PVP) at rest	Peripheral venous pressure (PVP) at rest will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).	Baseline, 12 Weeks
Peripheral venous pressure (PVP) with feet elevated	Peripheral venous pressure (PVP) with feet elevated will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).	Baseline, 12 Weeks
Peripheral venous pressure (PVP) at 20W exercise	Peripheral venous pressure (PVP) at 20W exercise will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).	Baseline, 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output at rest	Cardiac output measures the amount of blood the heart pumps per minute. It is calculated by Cardiac Output= Oxygen Consumption/(Arterial - Venous Oxygen Content Difference). Cardiac output will be measured in liters per minute (L/min).	Baseline, 12 Weeks
Cardiac output with exercise	Cardiac output measures the amount of blood the heart pumps per minute. It is calculated by Cardiac Output= Oxygen Consumption/(Arterial - Venous Oxygen Content Difference). Cardiac output will be measured in liters per minute (L/min).	Baseline, 12 Weeks
Peak oxygen consumption (VO2) during exercise	Peak oxygen consumption (VO2) is measured in milliliters of oxygen per minute (mL/min).	Baseline, 12 Weeks
Change in plasma volume	Plasma volume will be determined by radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY). Plasma volume will be measured in milliliters (mL).	Baseline, 12 Weeks
Change in blood volume	Blood volume will be determined by radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY). Blood volume will be measured in milliliters (mL).	Baseline, 12 Weeks
SF-36 quality of life (QOL)	SF-36 quality of life (QOL) questionnaire is a 36-question questionnaire that evaluates a patient's quality of life. The score range is from 0-100, with a higher score reflecting a better quality of life.	Baseline, 12 Weeks
Change in fat mass	Fat mass will be determined by Dual Energy X-ray Absorptiometry Scan. Fat mass will be measured in kilograms (kg).	Baseline, 12 Weeks
Change in fat free mass	Fat free mass will be determined by Dual Energy X-ray Absorptiometry Scan. Fat free mass will be measured in kilograms (kg).	Baseline, 12 Weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Luke Burchill, M.B.B.S., Ph.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 2, 2025
• First Submitted That Met QC Criteria: January 2, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Fontan; SGLT2 inhibitors; HFpEF
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Univentricular Heart; Heart Diseases; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; dapagliflozin
• Other Study ID Numbers: 24-011044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No