Dapagliflozin for Heart Failure

(FonDap Trial)

Overseen By Ari Cedars

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must not be taking: SGLT2 inhibitors

Disqualifiers: Pregnancy, Type 1 diabetes, Severe hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

29 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that there should be no planned changes in medical therapy for one month after enrollment. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug dapagliflozin for heart failure?

Dapagliflozin has been shown to reduce the risk of cardiovascular death or worsening heart failure in patients with heart failure with reduced ejection fraction (HFrEF), as demonstrated in the DAPA-HF trial. It is effective regardless of whether patients have type 2 diabetes, and it is generally well tolerated. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally well-tolerated in humans for conditions like heart failure and type 2 diabetes, with a consistent safety profile across different uses. Common side effects include a low risk of low blood sugar and genital infections, especially in women, and it is not recommended for people with moderate or severe kidney problems. ^{2 3 4 5 6}

How is the drug dapagliflozin unique in treating heart failure?

Dapagliflozin is unique because it is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that not only helps manage blood sugar levels in type 2 diabetes but also significantly reduces the risk of cardiovascular death or hospitalization for heart failure, even in patients without diabetes. This makes it a valuable addition to heart failure treatments, offering benefits beyond traditional heart failure medications. ^{2 3 4 5 7}

Research Team

Ari Cedars

Principal Investigator

Johns Hopkins University

Eligibility Criteria

Adults aged ≥18 with Fontan circulation, stable for the past 6 months, and not expecting to change their medication or undergo any procedures within a month of enrollment. Women must use effective contraception or be non-fertile; men should also use barrier contraception during the study and for three months after.

Inclusion Criteria

You must provide your consent before any procedures related to the study.

No alterations to medical therapy are anticipated within the first month of enrollment.

You must have been clinically stable for the past 6 months (as determined by the Principal Investigator).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive daily oral use of Dapagliflozin 10mg tablet for 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

2 follow-up phone calls

Treatment Details

Interventions

• Dapagliflozin

Trial Overview The trial is testing if Dapagliflozin can prevent worsening heart failure in adults with Fontan circulation by checking its effects on Fontan pressure and exercise capacity. It includes health assessments, blood tests, physical exams, exercise tests, safety calls, and home blood pressure monitoring over five weeks.

Participant Groups

Group I: Dapagliflozin Experimental Treatment 1 Intervention

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

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Brett Boyer Foundation

Collaborator

Trials

1

Recruited

30+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

Dapagliflozin significantly reduces the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF and reduced ejection fraction, with benefits becoming apparent as early as 28 days after starting treatment.

Patients who had been hospitalized for HF more recently experienced greater reductions in risk, indicating that dapagliflozin may be particularly effective for those at higher risk due to recent hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction. Berg, DD., Jhund, PS., Docherty, KF., et al.[2022]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin (Forxiga) is no longer authorized for the treatment of type 1 diabetes mellitus, indicating a significant change in its regulatory status.

This decision reflects safety concerns or efficacy issues that may have arisen from clinical evaluations or post-marketing surveillance, emphasizing the importance of ongoing drug safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

7. Belgium pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. [2021]