The Fontan Dapagliflozin Pilot Study

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this clinical trial is to study if an investigational study drug called Dapagliflozin could prevent heart failure from getting worse in adults with Fontan circulation. The main questions it aims to answer are:

1. Does Dapagliflozin decrease Fontan pressure?

2. Does Dapagliflozin improve exercise capacity and heart failure symptoms?

Participants will have 4 study visits and 2 follow-up phone calls. The total duration of participation in the study will be up to 5 weeks from the time of screening to the completion of the final safety evaluation. Study procedures include the collection of study-related health information and blood samples, physical examination, exercise testing, total body water assessment, blood laboratory testing, health status survey, safety evaluation phone calls, and home blood pressure monitoring.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Collaborators: AstraZeneca; Brett Boyer Foundation; University of California, Los Angeles
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

For inclusion in the study subjects should fulfil the following criteria based on local regulations:

1. Provision of informed consent prior to any study specific procedures

2. Female and/or male subjects aged ≥18 years

3. Subjects with Fontan circulation (in the opinion of the PI)

4. Subjects with clinical stability for 6 months preceding enrollment (in the opinion of the PI)

5. Subjects with no planned changes in medical therapy in the 1 months after enrollment

6. Subjects with no planned interventional procedures in the 1 months after enrollment

7. Negative pregnancy test (urine or serum) for female subjects of childbearing potential.

8. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time the subjects sign consent) and for 3 months after the last dose of Drug A/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

9. Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time the subjects sign consent) and for 3 months after the last dose of Drug A/matching placebo to prevent pregnancy in a partner.

10. Subjects who are blood donors should not donate blood during the study and for 3 months following the subject's last dose of dapagliflozin.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)

2. Previous enrollment or randomisation in the present study

3. Participation in another clinical study with an investigational product during the last 6 months

4. Pregnancy or breast feeding or desire to become pregnant or breast feed during the study period

5. Hospitalization within 6 months prior to enrollment

6. Arrhythmia requiring change in therapy within 6 months prior to enrollment

7. Interventional procedure of any kind (including cardioversion) within 6 months prior to enrollment

8. Difficulty with upper extremity IV placement in the past

9. Known obstruction anywhere within the venous circulation including at the level of the Glenn or Fontan anastomosis or within the pulmonary vasculature.

10. Symptomatic hypotension or systemic systolic blood pressure of <95 millimeters of mercury (mmHg)

11. Estimated glomerular filtration rate of <25ml per minute per 1.73m2 body surface area as assessed by Modification of Diet in Renal Disease (MDRD) calculation

12. Prior use of SGLT2 inhibitors with intolerable side effects

13. Type 1 diabetes

14. Inability to comply with the study protocol

15. Lack of English-proficiency

16. History of hypersensitivity to SGLT2 inhibitors

17. Severe hepatic impairment defined as a Model for End-stage Liver Disease (MELD) XI score of >10