Dapagliflozin for Fontan Circulation

Overseen By Yusef Maarouf

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Insulin, Pramlintide, Empagliflozin, others

Disqualifiers: Type I diabetes, Recent hospitalization, Significant valvular heart disease, Severe kidney disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dapagliflozin, an SGLT2 inhibitor, to determine its effect on blood flow in individuals with failing Fontan circulation, a condition affecting those who have undergone a specific heart surgery. The researchers aim to discover if the drug can lower lung pressure at rest and during exercise, potentially improving breathing and overall heart function. Participants will receive either dapagliflozin or a placebo, which contains no active ingredients. The trial is suitable for adults who have had the Fontan procedure, experience shortness of breath not caused by other conditions, and have elevated lung pressure during exercise. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including Insulin, Pramlintide, Sandostatin, Akeega, Growth Hormone, Lithium, Chloroquine, Hydroxychloroquine, Thioctic acid, Empagliflozin, and Canagliflozin. If you are on any of these, you would need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dapagliflozin is generally safe for adults. One study found that people taking dapagliflozin did not experience major short-term side effects, and their kidney function remained stable. Another study found that dapagliflozin lowered the risk of a specific type of kidney injury by 30%, suggesting safety for certain heart conditions. Additionally, in adults who underwent a Fontan procedure, dapagliflozin helped reduce fluid buildup without causing serious side effects. This evidence suggests dapagliflozin may be a safe option for individuals with heart issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dapagliflozin is unique because it targets the kidneys to help remove excess sodium and water, which can improve heart function in people with Fontan circulation. Unlike standard treatments that primarily focus on managing symptoms and preventing complications, dapagliflozin offers a new mechanism of action by being a sodium-glucose co-transporter 2 (SGLT2) inhibitor. This approach not only helps with fluid management but might also provide additional cardiovascular benefits, making it an exciting prospect for improving the quality of life for those affected by this condition.

What evidence suggests that dapagliflozin might be an effective treatment for failing Fontan circulation?

Research has shown that dapagliflozin can help with heart problems. The DAPA-HF study found that it lowered the risk of worsening heart failure and reduced the chance of dying from heart-related issues compared to a placebo. In this trial, participants will receive either dapagliflozin or a placebo. For patients with Fontan circulation, a specific heart condition, dapagliflozin reportedly increased urine output and reduced swelling. These results suggest that dapagliflozin might help manage problems related to failing Fontan circulation by improving heart function and reducing fluid buildup. ^{1 2 4 6 7}

Who Is on the Research Team?

Luke Burchill, M.B.B.S., Ph.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with a type of heart condition known as failing Fontan circulation, which can occur in people who have had surgery to correct single ventricle heart defects. Participants should be able to perform exercise tests.

Inclusion Criteria

I experience shortness of breath not caused by heart issues.

Signed informed consent prior to any study specific procedures

I am either male or female.

Exclusion Criteria

I do not have serious heart valve problems.

I have a heart condition with a specific blood flow blockage.

I have a heart condition not caused by other diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin or placebo for 6 months to assess effects on pulmonary capillary wedge pressure

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study is testing if dapagliflozin, a medication typically used for diabetes, can help reduce the pressure in lung blood vessels at rest and during exercise over six months compared to a placebo (a tablet with no active drug).

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Dapagliflozin is an effective treatment for type 2 diabetes, showing noninferiority to metformin and glimepiride in clinical trials involving 9 studies, indicating it can be a reliable option for patients.

While generally safe, dapagliflozin is associated with an increased risk of urinary infections and other side effects, suggesting it may be best used as an add-on therapy for patients not adequately controlled on other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. Aylsworth, A., Dean, Z., VanNorman, C., et al.[2019]

Dapagliflozin, a selective SGLT2 inhibitor, has been shown to improve glycaemic control in adults with type 1 diabetes (T1D) and a BMI of ≥27 kg/m2, allowing for reduced insulin doses and weight loss over 24 weeks, with effects maintained up to 52 weeks.

The drug has a favorable safety profile, with a lower incidence of diabetic ketoacidosis in patients with higher BMI compared to the overall population, making it a promising adjunct treatment for those not achieving adequate control with insulin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Type 1 Diabetes. Paik, J., Blair, HA.[2021]

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, when added to standard treatment for heart failure with reduced ejection fraction (HFrEF), significantly improves patient outcomes, increasing quality-adjusted life years (QALYs) from 6.33 to 6.92, while the cost of treatment rises from approximately 559 USD to 1745 USD.

The cost-effectiveness analysis shows that dapagliflozin is a cost-effective option for HFrEF patients, with an incremental cost-effectiveness ratio (ICER) of 1991 USD/QALY, and it remains cost-effective for 87% of scenarios at a willingness to pay threshold of 5131 USD/QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-utility analysis of add-on dapagliflozin treatment in heart failure with reduced ejection fraction. Krittayaphong, R., Permsuwan, U.[2021]

In a study involving over 34,000 person-years of real-world exposure, dapagliflozin was associated with a significantly lower incidence of hospitalization for acute kidney injury (hAKI) compared to other glucose-lowering drugs, indicating a safer profile for kidney function.

The adjusted incidence rate ratios showed that dapagliflozin users had a 30% reduced risk of hAKI, supporting its safety and efficacy in treating type 2 diabetes mellitus without compromising kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting. Johannes, CB., Beachler, DC., Layton, JB., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05741658

NCT05741658 | The Fontan Dapagliflozin Pilot Study This study is designed to define more closely the physiologic changes which dapagliflozin create in the Fontan circulation, with the goal of providing data in ...

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

Feasibility and Safety of Sodium Glucose Cotransporter-2 ... ... effects on patients with the Fontan circulation were still unclear. All patients had increased urinary output and reduced oedema and/or ...

3. withpower.com withpower.com/trial/dapagliflozin-for-fontan-circulation-0a3ee

Dapagliflozin for Fontan Circulation In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06762964?draw=2&rank=1

Dapagliflozin in the Failing Fontan Circulation The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 6 months affects pulmonary capillary wedge pressure ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666668525000394

Echocardiographic effects of sodium-glucose cotransporter ... The median age was 21 [20–42] years, 8 (61.5 %) were female, 10 (76.9 %) had a Fontan circulation, 8 (61.5 %) had SVFrEF, and 5 (38.5 %) SVFpEF at the start of ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666668524000041

Safety of SGLT-2 inhibitors in the management of heart ... We found that initiation of SGLT2i was well tolerated during short term follow up. Specifically, there was no significant worsening of renal function or ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/pdf/10.1155/2022/5243594

Feasibility and Safety of Sodium Glucose Cotransporter‐2 ... We presented five adults after the. Fontan procedure who were treated with SGLT-2 inhibitors. All patients reduced oedema and/or pleural effusion despite other.