Dapagliflozin for Chronic Kidney Disease

Overseen by Rupal Mehta, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Northwestern University

Must be taking: Diuretics, ACE inhibitors

Must not be taking: SGLT2 inhibitors

Disqualifiers: Diabetes, Angina, Cancer, others

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing dapagliflozin, a medication that helps remove sugar from the body through urine, in patients with chronic kidney disease and early heart failure. The study aims to see if this medication can improve their heart and lung function by lowering blood sugar levels. Dapagliflozin was initially approved for type 2 diabetes and later found to reduce cardiovascular and kidney problems.

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.

What data supports the effectiveness of the drug Dapagliflozin for chronic kidney disease?

Dapagliflozin (Farxiga) is approved to reduce the risk of worsening kidney function, kidney failure, and heart-related issues in adults with chronic kidney disease, whether or not they have type 2 diabetes. ^{1 2 3 4 5}

Is dapagliflozin safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally well tolerated in humans, with a low risk of low blood sugar (hypoglycemia) and common side effects like genital infections. It is not recommended for people with moderate or severe kidney problems. ^{3 4 5 6 7}

How is the drug dapagliflozin unique for treating chronic kidney disease?

Dapagliflozin is unique because it is an oral medication originally used for type 2 diabetes that also helps reduce the risk of kidney function decline, kidney failure, and heart-related issues in people with chronic kidney disease, even if they don't have diabetes. It works by inhibiting a protein that helps the kidneys reabsorb glucose, which is different from other treatments for kidney disease. ^{2 3 4 8 9}

Research Team

Rupal Mehta, MD

Principal Investigator

Northwestern Univeristy

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dapagliflozin (Sodium-glucose transport protein 2 inhibitor)

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.

Participant Groups

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+

Dr. Jeffrey Sherman

Northwestern University

Chief Medical Officer

MD from Northwestern University

Dr. Alicia Löffler

Northwestern University

Chief Executive Officer since 2010

PhD from the University of Massachusetts at Amherst, post-doctoral training at Caltech

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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 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 (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 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 (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 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, 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 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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

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

Dapagliflozin in people with chronic kidney disease. [2023]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

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

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

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

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

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

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