Dapagliflozin for Chronic Kidney Disease

Overseen By Tamara Isakova, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Northwestern University

Must be taking: Diuretics, ACE inhibitors

Must not be taking: SGLT2 inhibitors

Disqualifiers: Diabetes, Angina, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 6

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug dapagliflozin affects heart and lung function in people with chronic kidney disease. Researchers aim to determine how this medication, when added to standard treatments, influences the body’s natural processes. Participants will either receive dapagliflozin or continue their usual care for six months. The trial seeks individuals with chronic kidney disease and stable heart function, without diabetes or significant lung issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 must not be on sodium-glucose cotransporter 2 inhibitor therapy. You should be on stable doses of diuretics and/or certain blood pressure medications.

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

Research has shown that dapagliflozin is generally safe for people with chronic kidney disease (CKD). In one study, fewer participants died in the dapagliflozin group compared to the placebo group, suggesting it might help some patients live longer. Another study found no cases of diabetic ketoacidosis, a serious condition, in those taking dapagliflozin, regardless of whether they had type 2 diabetes.

Short-term use of dapagliflozin in CKD patients proved safe, with most individuals experiencing no major problems. Dapagliflozin's approval for other conditions further supports its overall safety.

These findings suggest that dapagliflozin is well-tolerated by many CKD patients, with few serious side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for chronic kidney disease focus on managing symptoms and slowing progression, often involving blood pressure medications or dietary changes. But dapagliflozin works differently, targeting the kidneys directly to help them remove excess glucose and sodium. This mechanism not only helps control blood sugar levels but also reduces the strain on the kidneys, potentially slowing the disease's progression. Researchers are excited about dapagliflozin because it offers a dual benefit for both kidney function and cardiovascular health, which is crucial for patients with chronic kidney disease.

What evidence suggests that dapagliflozin might be an effective treatment for chronic kidney disease?

Research has shown that dapagliflozin, which participants in this trial may receive, can help slow chronic kidney disease (CKD). Studies have found it can delay kidney failure by about 6.6 years. In one major study, dapagliflozin lowered the risk of worsening kidney disease or death related to it. This treatment aids the kidneys by managing blood sugar and reducing stress on them. Overall, dapagliflozin has shown promising results in improving kidney function and reducing complications in CKD patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Rupal Mehta, MD

Principal Investigator

Northwestern Univeristy

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic kidney disease who are on stable heart medication, have signs of a specific type of heart failure but no symptoms, and an eGFR between 25-60. It's not for those with liver disease, recent heart procedures, extreme blood pressure levels, pregnancy, certain systemic diseases like amyloidosis or sarcoidosis, diabetes, severe lung disease requiring oxygen therapy or significant chest pain.

Inclusion Criteria

My heart test shows early signs of heart failure but it can still pump well.

I am on a stable dose of medication for my blood pressure or heart condition.

I am older than 18 years.

Exclusion Criteria

I currently have active cancer.

My heart pumps less blood than normal.

I do not have any chronic conditions that would prevent me from completing heart tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin or standard of care for six months

6 months

Baseline and 6-month visits for metabolomic and cardiac testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study tests the effects of Dapagliflozin (Farxiga), a drug that affects sugar transport in kidneys when added to standard care. It focuses on how this drug influences heart and lung function as well as metabolites in patients with chronic kidney disease.

How Is the Trial Designed?

Group I: Intervention group Experimental Treatment 1 Intervention

Thirty individuals will be randomized to dapagliflozin 10mg to be taken daily for six months.

Group II: Standard of Care group Active Control 1 Intervention

Thirty individuals will be randomized to standard of care treatment.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

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 (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 has been shown to be effective in improving outcomes for patients with chronic kidney disease, as highlighted in the commentary on a study involving diverse patient populations.

The commentary emphasizes the importance of dapagliflozin's mechanism of action, which includes reducing the risk of kidney disease progression and cardiovascular events, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin in people with chronic kidney disease. Sylvester, RD., Khong, TK.[2023]

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 (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 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 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 has been shown to significantly improve kidney outcomes in patients with chronic kidney disease, demonstrating its efficacy in reducing the risk of kidney disease progression.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of dapagliflozin in managing chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality. Molony, DA., LeMaistre, FI.[2021]

Citations

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

The long-term effects of dapagliflozin in chronic kidney ... Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) ...

2. farxiga-hcp.com farxiga-hcp.com/chronic-kidney-disease

Chronic Kidney Disease | FARXIGA® (dapagliflozin) 5 mg ... The primary efficacy endpoint was a composite of sustained ≥50% eGFR decline, ESKD, or CV or renal death. 97% of patients received a stable dose of ACEi/ARB ...

3. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2021/farxiga-approved-in-the-us-for-ckd.html

Farxiga approved in the US for the treatment of chronic ... In August 2020, results from the DAPA-CKD Phase III trial demonstrated that Farxiga achieved unprecedented reduction in the composite risk of ...

4. academic.oup.com academic.oup.com/ndt/article/39/12/2040/7668437

The long-term effects of dapagliflozin in chronic kidney disease Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39834621/

Efficacy and safety of dapagliflozin in patients with CKD We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD ...

7. hfsa.org hfsa.org/farxiga-demonstrated-unprecedented-reduction-risk-kidney-failure-and-cardiovascular-or-renal-death

Farxiga demonstrated unprecedented reduction in the risk ... Farxiga is the first medicine to significantly prolong survival in a renal outcomes trial in patients with chronic kidney disease with and without type-2 ...