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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Dapagliflozin (also known as Farxiga or Forxiga) can prevent heart failure from worsening in adults with Fontan circulation, a unique congenital heart condition. Researchers aim to determine if the drug can lower heart pressure and improve exercise capacity and symptoms. The trial lasts about five weeks and includes health checks, exercise tests, and home blood pressure monitoring. Individuals with Fontan circulation who have been stable for six months and have no planned changes in their medical treatment may be suitable candidates for this study. As a Phase 4 trial, the research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for Dapagliflozin?

Research has shown that dapagliflozin is generally well-tolerated by patients with heart failure. In studies, fewer patients taking dapagliflozin experienced worsening heart failure compared to those not taking the drug. Specifically, only 10% of patients on dapagliflozin had a worsening event, compared to 13.7% of those on a placebo.

Additionally, dapagliflozin helps patients live longer and reduces the risk of death from heart-related issues and hospital visits due to heart failure. Another study focused on patients with Fontan circulation, a specific heart condition, confirmed that dapagliflozin is safe for them.

Overall, the safety data for dapagliflozin in heart failure patients is positive, with only a small percentage experiencing serious problems. This suggests that dapagliflozin could be a safe option for managing heart failure symptoms, especially for those with specific heart conditions like Fontan circulation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Dapagliflozin is unique because it offers a novel approach to managing heart failure, especially in adults with Fontan circulation. Unlike traditional treatments that focus on managing symptoms or improving heart muscle function, Dapagliflozin works by inhibiting a protein called SGLT2, which helps the body get rid of excess glucose and sodium through urine. This mechanism not only helps in reducing fluid overload but also provides additional cardiovascular benefits, potentially improving heart health in a different way compared to existing options. Researchers are excited about this treatment because it could offer a new avenue for heart failure patients, particularly those with complex circulations like Fontan, who may not fully benefit from conventional therapies.

What is the effectiveness track record for Dapagliflozin in treating heart failure?

Research shows that dapagliflozin, which participants in this trial will receive, effectively treats heart failure. Studies have found that it can reduce the risk of hospitalization for heart failure by about 24%. It also lowers the chance of dying from heart-related issues by 14% and from any cause by 10%. Additionally, dapagliflozin improves heart failure symptoms and physical limitations over time. This makes it a promising option for people with heart failure, including those with special conditions like Fontan circulation. ^{6 7 8 9 10}

Who Is on the Research Team?

Ari Cedars

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 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 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]

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 (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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10453961/

Effect of Dapagliflozin in Patients with Heart Failure

Additionally, dapagliflozin significantly reduced the hospitalization due to heart failure (RR = 0.76, 95% CI: 0.70–0.84, P > 0.00001, I2 = 0%) ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2206286

Dapagliflozin in Heart Failure with Mildly Reduced or ...

Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ...

3.

astrazeneca-us.com

astrazeneca-us.com/media/press-releases/2022/new-data-show-farxiga-significantly-lowers-the-risk-of-cardiovascular-death-in-patients-with-heart-failure.html

New data show FARXIGA significantly lowers the risk of ...

Pre-specified pooled analysis from Phase III trials demonstrated reduction in CV death by 14% and reduction in death from any cause by 10% ...

4.

jacc.org

jacc.org/doi/10.1016/j.jchf.2024.11.023

Severe Heart Failure and Treatment With Dapagliflozin ...

Dapagliflozin decreased the risk of clinical outcomes regardless of severe HF status and LVEF category, and it was safe and well tolerated. The data support the ...

5.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.122.009837

Dapagliflozin Improves Heart Failure Symptoms and ...

Dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across ...

6.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.076575

Dapagliflozin in Patients Hospitalized for Heart Failure

Cardiovascular death occurred in 30 (2.5%) and 37 (3.1%) patients (HR, 0.78; 95% CI, 0.48-1.27), and death from any cause occurred in 36 (3.0%) ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05741658

NCT05741658 | The Fontan Dapagliflozin Pilot Study

Also called a data safety and monitoring board, or DSMB. ... Dapagliflozin could prevent heart failure from getting worse in adults with Fontan circulation.

8.

farxiga-hcp.com

farxiga-hcp.com/heart-failure

Heart Failure | FARXIGA® (dapagliflozin) 5 mg & 10 mg tablets

FARXIGA helps patients live longer and stay out of the hospital by reducing the risk of CV death and hospitalization for HF 1-3.

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9757934/

Feasibility and Safety of Sodium Glucose Cotransporter-2 ...

Our case series supported the feasibility and safety of SGLT-2 inhibitors in patients with Fontan circulatory failure, although the exact changes in urinary ...

10.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1911303

Dapagliflozin in Patients with Heart Failure and Reduced ...

A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio ...