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

Trial Summary

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.

What data supports the effectiveness of the drug Dapagliflozin for Fontan circulation?

While there is no direct evidence for Dapagliflozin in Fontan circulation, similar treatments for pulmonary hypertension, like bosentan, have shown benefits in improving exercise capacity and outcomes in Fontan patients. This suggests that drugs targeting pulmonary circulation issues might be beneficial for Fontan patients. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin has been studied for various conditions like type 2 diabetes, heart failure, and type 1 diabetes, and is generally well tolerated with a safety profile consistent across these conditions. Some studies noted potential concerns like kidney function effects, but overall, it is considered safe with manageable side effects. ^{6 7 8 9 10}

How is the drug dapagliflozin unique for treating Fontan circulation?

Dapagliflozin is unique because it is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, originally used to manage diabetes and heart failure, and it works by reducing blood sugar levels and improving heart function. Its use in Fontan circulation is novel, as there are no standard treatments specifically for this condition, making dapagliflozin a potentially valuable option. ^{8 9 11 12 13}

What is the purpose of this trial?

The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 6 months affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in adults with failing Fontan circulation.

Research Team

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

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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, 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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Outcomes after initial heart failure consultation in Fontan patients. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Fontan and the pulmonary circulation: a potential role for new pulmonary hypertension therapies. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[Efficacy of endothelin receptor antagonist bosentan on the long-term prognosis in patients after Fontan operation]. [2018]

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

The effect of bosentan in patients with a failing Fontan circulation. [2018]

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

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. [2019]

7. New Zealand 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. [2023]

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

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

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

Dapagliflozin: A Review in Type 1 Diabetes. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety of dapagliflozin in a broad population of patients with type 2 diabetes: Analyses from the DECLARE-TIMI 58 study. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Influence of background medical therapy on efficacy and safety of dapagliflozin in patients with heart failure with improved ejection fraction in the DELIVER trial. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Eligibility for dapagliflozin in unselected patients hospitalised with decompensated heart failure. [2022]