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

Trial Summary

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.

What data supports the effectiveness of the drug Dapagliflozin for Cardio-Renal Syndrome?

Dapagliflozin is effective in reducing the risk of kidney problems and heart-related issues in people with chronic kidney disease, whether or not they have type 2 diabetes. It also helps in managing heart failure and lowering blood sugar levels in type 2 diabetes, showing benefits for both heart and kidney health. ^{1 2 3 4 5}

Is dapagliflozin safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally well-tolerated and has a consistent safety profile across various conditions, including type 2 diabetes and heart failure. It is approved for reducing risks related to kidney and heart issues, and its safety has been evaluated in multiple studies. ^{1 2 3 6 7}

How does the drug dapagliflozin differ from other treatments for cardio-renal syndrome?

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 provides cardiovascular and kidney protection. It reduces the risk of heart failure and kidney disease progression, making it a novel option for patients with cardio-renal syndrome. ^{1 2 3 4 8}

What is the purpose of this trial?

The long-term objective of this study is to test whether the addition of SGLT2 inhibitors to usual care during acute heart failure management in patients who develop kidney injury shortens the time to achieving symptomatic improvement and kidney function recovery. The study aims to assess feasibility and acceptability of such a randomized clinical trial.

Research Team

Abinet Aklilu

Principal Investigator

Yale University

Perry Wilson

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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 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]

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 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]

References

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

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

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

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

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

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

4. Belgium pubmed.ncbi.nlm.nih.gov

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

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

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

6. United States 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. [2022]

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

8. Spain pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. [2022]