The Fontan Dapagliflozin Pilot Study

NCT05741658 | Enrolling By Invitation Phase 4 FDA Drug

• 2 other identifiers: IRB00254477ESR-21-21445
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 1.Does Dapagliflozin decrease Fontan pressure?
2. 2.Does Dapagliflozin improve exercise capacity and heart failure symptoms?

Conditions

Heart Failure

Keywords

Fontan; Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors; Heart failure

Outcome Measures

Primary Outcomes (1)

• Peripheral venous pressure (millimeters of mercury) at rest measured by manometry

  To investigate the impact of Dapagliflozin on changing central venous pressure in Fontan patients

  From baseline at week 0 and to follow up at week 4

Secondary Outcomes (7)

• Total body water (liter) as measured by bioelectrical impedance analyzer

  From baseline at week 0 and to follow up at week 4

• Maximal oxygen uptake (milliliters/kilograms/minutes) as measured by cardiopulmonary exercise test

  From baseline at week 0 and to follow up at week 4

• oxygen pulse (milliliters oxygen per beat per kilogram) as measured by cardiopulmonary exercise test

  From baseline at week 0 and to follow up at week 4

• ventilator efficiency slope (no unit) as measured by cardiopulmonary exercise test

  From baseline at week 0 and to follow up at week 4

• oxygen uptake efficiency slope (no unit) as measured by cardiopulmonary exercise test

  From baseline at week 0 and to follow up at week 4

Study Arms (1)

Dapagliflozin

OTHER

4-week, Daily Oral Use of Dapagliflozin 10mg Tablet in Adults with Fontan Circulation

Drug: Dapagliflozin 10mg Tab

Interventions

Dapagliflozin 10mg Tab DRUG

Participants will take one Dapagliflozin 10mg tablet once per day for 4 weeks.

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Female and/or male subjects aged ≥18 years
• Subjects with Fontan circulation (in the opinion of the PI)
• Subjects with clinical stability for 6 months preceding enrollment (in the opinion of the PI)
• Subjects with no planned changes in medical therapy in the 1 months after enrollment
• Subjects with no planned interventional procedures in the 1 months after enrollment
• Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
• 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.
• 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.
• Subjects who are blood donors should not donate blood during the study and for 3 months following the subject's last dose of dapagliflozin.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Previous enrollment or randomisation in the present study
• Participation in another clinical study with an investigational product during the last 6 months
• Pregnancy or breast feeding or desire to become pregnant or breast feed during the study period
• Hospitalization within 6 months prior to enrollment
• Arrhythmia requiring change in therapy within 6 months prior to enrollment
• Interventional procedure of any kind (including cardioversion) within 6 months prior to enrollment
• Difficulty with upper extremity IV placement in the past
• Known obstruction anywhere within the venous circulation including at the level of the Glenn or Fontan anastomosis or within the pulmonary vasculature.
• Symptomatic hypotension or systemic systolic blood pressure of \<95 millimeters of mercury (mmHg)
• 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
• Prior use of SGLT2 inhibitors with intolerable side effects
• Type 1 diabetes
• Inability to comply with the study protocol
• Lack of English-proficiency

Sponsors & Collaborators

• University of California, Los Angeles: collaborator
• Brett Boyer Foundation: collaborator
• AstraZeneca: collaborator
• Johns Hopkins University: lead

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Related Publications (16)

• Akintoye E, Miranda WR, Veldtman GR, Connolly HM, Egbe AC. National trends in Fontan operation and in-hospital outcomes in the USA. Heart. 2019 May;105(9):708-714. doi: 10.1136/heartjnl-2018-313680. Epub 2018 Oct 30.

  PMID: 30377261 BACKGROUND

• Rychik J, Atz AM, Celermajer DS, Deal BJ, Gatzoulis MA, Gewillig MH, Hsia TY, Hsu DT, Kovacs AH, McCrindle BW, Newburger JW, Pike NA, Rodefeld M, Rosenthal DN, Schumacher KR, Marino BS, Stout K, Veldtman G, Younoszai AK, d'Udekem Y; American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing. Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association. Circulation. 2019 Aug 6;140(6):e234-e284. doi: 10.1161/CIR.0000000000000696. Epub 2019 Jul 1.

  PMID: 31256636 BACKGROUND

• Rychik J. Forty years of the Fontan operation: a failed strategy. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13(1):96-100. doi: 10.1053/j.pcsu.2010.02.006. No abstract available.

  PMID: 20307870 BACKGROUND

• McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.

  PMID: 31535829 BACKGROUND

• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

  PMID: 26378978 BACKGROUND

• Radholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, Fulcher G, Barrett TD, Shaw W, Desai M, Matthews DR, Neal B. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program. Circulation. 2018 Jul 31;138(5):458-468. doi: 10.1161/CIRCULATIONAHA.118.034222.

  PMID: 29526832 BACKGROUND

• Figtree GA, Radholm K, Barrett TD, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Neal B. Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2591-2593. doi: 10.1161/CIRCULATIONAHA.119.040057. Epub 2019 Mar 17. No abstract available.

  PMID: 30882240 BACKGROUND

• Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020 Sep 15;142(11):1028-1039. doi: 10.1161/CIRCULATIONAHA.120.045691. Epub 2020 May 15.

  PMID: 32410463 BACKGROUND

• Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.

  PMID: 28605608 BACKGROUND

• Packer M, Anker SD, Butler J, Filippatos G, Zannad F. Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure: Proposal of a Novel Mechanism of Action. JAMA Cardiol. 2017 Sep 1;2(9):1025-1029. doi: 10.1001/jamacardio.2017.2275.

  PMID: 28768320 BACKGROUND

• Koyani CN, Plastira I, Sourij H, Hallstrom S, Schmidt A, Rainer PP, Bugger H, Frank S, Malle E, von Lewinski D. Empagliflozin protects heart from inflammation and energy depletion via AMPK activation. Pharmacol Res. 2020 Aug;158:104870. doi: 10.1016/j.phrs.2020.104870. Epub 2020 May 17.

  PMID: 32434052 BACKGROUND

• Packer M. Interplay of adenosine monophosphate-activated protein kinase/sirtuin-1 activation and sodium influx inhibition mediates the renal benefits of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: A novel conceptual framework. Diabetes Obes Metab. 2020 May;22(5):734-742. doi: 10.1111/dom.13961. Epub 2020 Feb 20.

  PMID: 31916329 BACKGROUND

• Cedars AM, Ko JM, John AS, Vittengl J, Stefanescu-Schmidt AC, Jarrett RB, Kutty S, Spertus JA. Development of a Novel Adult Congenital Heart Disease-Specific Patient-Reported Outcome Metric. J Am Heart Assoc. 2020 Jun 2;9(11):e015730. doi: 10.1161/JAHA.119.015730. Epub 2020 May 16.

  PMID: 32419592 BACKGROUND

• Tan W, Small A, Gallotti R, Moore J, Aboulhosn J. Peripheral venous pressure accurately predicts central venous pressure in the adult Fontan circulation. Int J Cardiol. 2021 Mar 1;326:77-80. doi: 10.1016/j.ijcard.2020.11.007. Epub 2020 Nov 13.

  PMID: 33189798 BACKGROUND

• Kushner RF, Schoeller DA. Estimation of total body water by bioelectrical impedance analysis. Am J Clin Nutr. 1986 Sep;44(3):417-24. doi: 10.1093/ajcn/44.3.417.

  PMID: 3529918 BACKGROUND

• Bedogni G, Malavolti M, Severi S, Poli M, Mussi C, Fantuzzi AL, Battistini N. Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water. Eur J Clin Nutr. 2002 Nov;56(11):1143-8. doi: 10.1038/sj.ejcn.1601466.

  PMID: 12428182 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Ari Cedars

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: February 23, 2023
• Study Start: November 8, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)