Dapagliflozin for Cardio-Renal Syndrome

(SGLT2i in CRS Trial)

Overseen By Perry Wilson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: SGLT2 inhibitors

Must not be taking: Investigational heart drugs

Disqualifiers: Pregnancy, Advanced kidney disease, 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: Unknown

Duration: 3 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding dapagliflozin to regular heart failure care can improve symptoms and kidney function more quickly for those with kidney injury during heart failure. Dapagliflozin, an SGLT2 inhibitor, helps manage heart and kidney issues. The study compares usual care to usual care plus dapagliflozin. Individuals with heart failure, not currently on SGLT2 inhibitors, and who have experienced kidney injury might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on an SGLT2 inhibitor or another investigational drug for heart failure within 72 hours before the study.

Is there any evidence suggesting that dapagliflozin is likely to be safe for humans?

Research shows that dapagliflozin is usually well-tolerated. Studies with patients who have chronic kidney disease found that dapagliflozin reduced the risk of kidney problems without causing major side effects. Another study found that it significantly lowered the risk of heart-related deaths and deaths from any cause in patients with heart failure. These findings suggest that dapagliflozin is safe for treating heart and kidney conditions. However, since this is a Phase 2 trial, the researchers aim to confirm its safety and effectiveness for new uses. Earlier tests have shown promise, but more information is needed to ensure its safety in this specific situation. ^{1 2 3 4}

Why do researchers think this study treatment might be promising?

Dapagliflozin is unique because it targets both the heart and kidneys by inhibiting the sodium-glucose cotransporter 2 (SGLT2), offering a dual benefit for patients with cardio-renal syndrome. Unlike traditional treatments that primarily focus on either heart or kidney function separately, dapagliflozin helps reduce blood sugar levels while also protecting the heart and kidneys. Researchers are excited because it has the potential to improve outcomes more comprehensively in a condition that affects multiple organ systems, all with a single treatment approach.

What evidence suggests that dapagliflozin might be an effective treatment for cardio-renal syndrome?

Research shows that dapagliflozin, which participants in this trial may receive, can improve heart and kidney health. Studies have found it reduces the risk of dying from heart-related issues by 14% in people with heart failure. It also slows the progression of kidney disease and delays other serious health problems. Dapagliflozin protects both the heart and kidneys, crucial for individuals with issues in both areas. This treatment has consistently proven helpful at various stages of heart and kidney disease. ^{2 3 5 6 7}

Who Is on the Research Team?

Perry Wilson

Principal Investigator

Yale University

Abinet Aklilu

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with heart failure, who can take oral medication and are willing to follow the study procedures. They must have a certain level of NT-proBNP in their blood, indicating heart stress. People on dialysis, pregnant or lactating women, those allergic to SGLT2 inhibitors, or with severe kidney issues cannot join.

Inclusion Criteria

Provision of signed and dated informed consent form

Your NT-proBNP level is higher than 300 pg/mL.

I am willing and able to follow the study rules and attend all appointments.

Exclusion Criteria

You have had low blood sugar without a clear reason in the last 30 days.

I am currently using or have used an SGLT2 inhibitor in the last 3 days.

Pregnancy or lactation (a pregnancy test will be performed prior to enrollment in women of child-bearing age)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 10 mg oral dose of dapagliflozin daily for three days or continue with usual care

3 days

Monitoring

Participants are monitored for changes in biomarkers of kidney injury, repair, and tubular function over five days

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including rehospitalization and mortality rates

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study tests if adding Dapagliflozin (an SGLT2 inhibitor) to standard care helps patients with acute heart failure recover faster regarding symptoms and kidney function. It evaluates how well this treatment works and its effects on early markers of kidney injury.

How Is the Trial Designed?

Group I: SGLT2i administration Experimental Treatment 1 Intervention

A 10 mg oral dose of dapagliflozin will be administered daily for three days.

Group II: Usual Care Active Control 1 Intervention

Subjects continue with usual care.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

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 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]

The fixed-dose combination of dapagliflozin and saxagliptin (QTERN) effectively reduces hemoglobin A1C levels in patients with uncontrolled type 2 diabetes when used alongside metformin, showing a significant difference in A1C reduction compared to other combinations.

QTERN is generally well tolerated, but its use may be limited by cost and modest efficacy in A1C reduction, highlighting the need for further research on its long-term effects on diabetes complications and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes. Coppenrath, VA., Hydery, T.[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 is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin, an SGLT2 inhibitor, is effective in treating type 2 diabetes and has been shown to significantly reduce cardiovascular and major renal events in clinical trials.

In the DAPA-CKD trial, dapagliflozin notably decreased the risk of kidney disease progression in patients with chronic kidney disease, making it a valuable treatment option for both diabetic and non-diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. Kelly, MS.[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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024816

Dapagliflozin in Patients with Chronic Kidney Disease The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.050391

Efficacy of Dapagliflozin on Renal Function and Outcomes ... There was no difference in the efficacy of dapagliflozin by baseline kidney function in preventing the risk of cardiovascular death or worsening ...

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% in patients with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38730538/

The long-term effects of dapagliflozin in chronic kidney ... Conclusion: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for ...

5. astrazeneca.com astrazeneca.com/media-centre/medical-releases/farxiga-demonstrated-consistent-benefit-regardless-of-heart-failure-duration-and-across-the-full-spectrum-of-cardiorenal-disease.html

Farxiga demonstrated consistent benefit regardless of ... Research has shown Farxiga's efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7078964/

The effects of dapagliflozin on cardio‐renal risk factors in ... Treatment with dapagliflozin over 24 weeks provides similar clinically relevant improvements in metabolic and haemodynamic parameters, and similar reductions ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7834909/

Efficacy of Dapagliflozin on Renal Function and Outcomes in ... There was no difference in the efficacy of dapagliflozin by baseline kidney function in preventing the risk of cardiovascular death or worsening heart failure.