Dapagliflozin for Kidney Complications

Overseen By Petter Bjornstad

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Immunosuppressants, Antihypertensives, GLP-1RA

Must not be taking: SGLT2 inhibitors, Anticoagulants

Disqualifiers: Type 1 diabetes, Heart failure, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dapagliflozin to determine its effects on heart and kidney health in individuals with a kidney transplant who also have type 2 diabetes or diabetes post-transplant. The trial compares dapagliflozin to a placebo (a pill with no active medicine) to assess its effectiveness. It seeks participants who had a kidney transplant at least a year ago, have stable diabetes and blood pressure, and regularly take certain medications. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective dapagliflozin can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that your current medications for immunosuppression, blood pressure, diabetes, and certain other conditions remain stable for at least 1-3 months before starting. If you're currently using SGLT2 inhibitors, you cannot participate.

What is the safety track record for dapagliflozin?

Studies have shown that dapagliflozin, the treatment being tested in this trial, is generally safe for people with chronic kidney disease. In earlier research, only about 2% of patients stopped using the drug due to side effects. The most common issues included sudden kidney problems and urinary tract infections. Importantly, dapagliflozin is already approved for other conditions, such as heart failure and chronic kidney disease, indicating it is well-tolerated by many people. Although limited information exists for kidney transplant recipients, these findings are promising for its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Dapagliflozin is unique because it targets kidney complications by inhibiting the sodium-glucose co-transporter 2 (SGLT2), a mechanism different from the usual blood pressure control or glucose management seen in traditional treatments like ACE inhibitors or ARBs. Researchers are excited about dapagliflozin because it not only helps manage blood sugar levels in people with diabetes but also offers protective benefits for the kidneys, potentially slowing down the progression of kidney disease. This dual action makes dapagliflozin a promising option for enhancing kidney health beyond the capabilities of current standard treatments.

What evidence suggests that dapagliflozin might be an effective treatment for kidney complications in kidney transplant recipients?

Research has shown that dapagliflozin, which participants in this trial may receive, can help slow chronic kidney disease. Studies have found that it can delay kidney failure by several years. Dapagliflozin also reduces the risk of serious kidney and heart problems, including death from heart-related issues. It works effectively regardless of the initial condition of the kidneys. This treatment is already approved for managing chronic kidney disease, demonstrating its effectiveness in improving kidney and heart health. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adult kidney transplant recipients aged 18-80 with stable blood pressure, diabetes management, and immunosuppression. Participants must have received their transplant at least a year ago and have specific levels of kidney function and protein in urine. It's not suitable for those who don't meet these health criteria or can't consent.

Inclusion Criteria

My kidney function, measured by eGFR, is between 30 and 90.

My urine protein levels are between 30 to 5000 mg/g.

I have type 2 diabetes or diabetes developed after a transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin 10mg daily or placebo for 12 months to assess efficacy and safety in improving cardiovascular and kidney graft function

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The study tests if Dapagliflozin, a drug that lowers sugar in the body, improves heart health and kidney function in people who got a new kidney but also have diabetes. Some will get the real medicine while others will take a placebo to compare results.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

Participants will receive dapagliflozin 10mg daily

Group II: Placebo Placebo Group 1 Intervention

Participants will receive one placebo tablet daily

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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 (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 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]

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, 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 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]

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. 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 ...

3. 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 ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05196347?term=NCT03036150%20NCT04492722%20NCT04724837%20NCT04794517%20NCT04930549%20NCT04991571%20NCT05196347%20NCT05250752%20NCT05359263%20NCT05570305%20NCT05884866&rank=5

Dapagliflozin and Renal Surrogate Outcomes in Advanced ... The goal of this study is to assess the efficacy and safety of dapagliflozin (Forxiga®, AstraZeneca) in reducing renal function progression and complications ...

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

Efficacy and safety of dapagliflozin in patients with CKD We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the ...

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

The long-term effects of dapagliflozin in chronic kidney disease In this population, dapagliflozin significantly reduced the incidence of hospitalization for heart failure and the renal composite endpoint.