Empagliflozin for Kidney Disease

(NDKD Trial)

Overseen By Shannen Ubalde, BS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Washington D.C. Veterans Affairs Medical Center

Must be taking: Empagliflozin

Must not be taking: Diabetes medications

Disqualifiers: Diabetes, Smoking, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Primary Objective:To study podocyte specific injury markers in African American Veterans with non-diabetic kidney disease(NDKD), on empagliflozin therapy. Primary Endpoint: Assess the effect of Empagliflozin on podocyte-specific proteins in exosomes isolated from subjects' urine, such as nephrin, podocalyxin and Wilms'Tumor (WT-1) protein. Secondary Objective: 1. Correlate changes in exosome-based podocyte specific proteins with standardized biomarkers of kidney injury including urine albumin/creatinine ratio (ACR) and estimated GFR. 2. Correlate systemic inflammatory markers (focusing on vascular and endothelial function) that are already established such as interleukins (IL1, IL6, IL-12) , hs-CRP and arterial stiffness measures with urine exosome-based podocyte protein estimation. 3. Correlate urine podocyte-specific protein markers with APOL1 mRNA expression levels in blood mononuclear cells (MNC)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on a statin, you need to be on a stable dose for a month. Also, you cannot participate if you are taking any diabetes medications.

What data supports the effectiveness of the drug empagliflozin for kidney disease?

Empagliflozin has been shown to reduce the progression of chronic kidney disease and lower the risk of cardiovascular issues in patients with type 2 diabetes and established cardiovascular disease. In the EMPA-REG Outcome trial, it significantly reduced the risk of cardiovascular death, hospitalization for heart failure, and worsening kidney problems. ^{1 2 3 4 5}

Is empagliflozin safe for people with kidney disease?

Empagliflozin (Jardiance) is generally considered safe for people, including those with chronic kidney disease (CKD), but it can have side effects like fluid deficits. It has been studied in patients with type 2 diabetes and CKD, showing it is well-tolerated, though specific safety data for Asians with CKD is still being explored. ^{2 6 7 8 9}

How does the drug empagliflozin differ from other treatments for kidney disease?

Empagliflozin is unique because it is a sodium-glucose co-transporter-2 (SGLT2) inhibitor that not only helps manage blood sugar levels in type 2 diabetes but also offers kidney and heart protection, reducing the progression of chronic kidney disease and cardiovascular risks. ^{1 2 4 7 10}

Research Team

Sabyasachi Sen, MD

Principal Investigator

Washington VA Medical Center

Eligibility Criteria

This trial is for African American veterans aged 20-90 with non-diabetic chronic kidney disease, specifically those who have a BMI of 25-45 and controlled blood pressure. They must have an eGFR between 30-90 mL/min/1.73 m2, albuminuria of at least 30 mg/g, and HbA1C levels below 6.5%. Participants need to be able to give informed consent.

Inclusion Criteria

BMI=25-39.9

Blood pressure controlled to ≤140/90

Ability to provide informed consent before any trial related activities are conducted

Exclusion Criteria

I have been diagnosed with diabetes.

Hypersensitivity to empagliflozin or any of the excipients in Jardiance, reactions such as angioedema

I have been diagnosed with Polycystic Kidney Disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Empagliflozin or placebo 10 mg orally daily to study podocyte specific injury markers

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Empagliflozin (SGLT2 Inhibitor)

Trial Overview The study tests the effect of Empagliflozin on proteins indicating podocyte injury in urine exosomes versus a placebo. It aims to see if this drug can improve markers related to kidney damage in patients without diabetes by comparing it with standard biomarkers like ACR and estimated GFR.

Participant Groups

Group I: Placebo Active Control 1 Intervention

Placebo 10 mg orally daily

Group II: Empagliflozin Active Control 1 Intervention

Empagliflozin 10 mg orally daily

Empagliflozin is already approved in Canada, Japan for the following indications:

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Washington D.C. Veterans Affairs Medical Center

Lead Sponsor

Trials

45

Recruited

18,500+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

The EMPA-KIDNEY study evaluated the effects of empagliflozin in patients with chronic kidney disease, demonstrating significant benefits in slowing the progression of kidney disease.

This study involved a large cohort of patients, providing robust evidence for the efficacy of empagliflozin as a treatment option for chronic kidney disease, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. Kwong, YD., Hsu, CY.[2023]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

In the EMPA-KIDNEY trial involving 6609 patients with chronic kidney disease, empagliflozin significantly reduced the risk of kidney disease progression or death from cardiovascular causes compared to placebo, with a hazard ratio of 0.72, indicating a 28% lower risk.

Patients taking empagliflozin also experienced fewer hospitalizations for any cause compared to those on placebo, suggesting a potential safety benefit, although there were no significant differences in heart failure hospitalizations or overall mortality between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin in Patients with Chronic Kidney Disease. Herrington, WG., Staplin, N., Wanner, C., et al.[2023]

In the EMPA-KIDNEY trial involving 6609 participants, empagliflozin significantly slowed the progression of chronic kidney disease, reducing the chronic decline in kidney function by 50% after an initial dip in eGFR.

The benefits of empagliflozin were observed across various patient groups, indicating that albuminuria levels should not be the sole factor in deciding treatment with SGLT2 inhibitors, as even patients with low albuminuria experienced significant improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

In the EMPA-REG Outcome trial involving 6952 patients with type 2 diabetes and established cardiovascular disease, empagliflozin significantly reduced the risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and worsening kidney disease by 39% compared to placebo.

The efficacy of empagliflozin was consistent across different Kidney Disease Improving Global Outcomes (KDIGO) risk categories, indicating that its benefits on cardiovascular and kidney outcomes were not influenced by the patients' baseline chronic kidney disease status, although it was associated with a higher rate of genital infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial. Levin, A., Perkovic, V., Wheeler, DC., et al.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

The EMPA-KIDNEY trial is a large-scale study involving 6609 participants with chronic kidney disease (CKD) to assess the efficacy and safety of empagliflozin in reducing the risk of kidney disease progression and cardiovascular death.

Participants included individuals with varying degrees of kidney function and both diabetic and non-diabetic patients, making the results applicable to a broad population at risk for CKD complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

In a study of 26,347 Asian patients with chronic kidney disease (CKD) and diabetes, empagliflozin significantly reduced major adverse cardiac events (MACEs), all-cause mortality, and other serious health issues compared to sitagliptin.

While empagliflozin showed overall safety and efficacy benefits, it was associated with a higher risk of genital tract infections, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Safety Analysis of Empagliflozin in Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease versus Normal Kidney Function: A Nationwide Cohort Study in Korea. Jang, HY., Kim, IW., Oh, JM.[2023]

Empagliflozin, when administered to 15,081 patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD), showed no new safety concerns, with similar rates of serious adverse events compared to placebo.

The treatment was associated with significantly lower risks of hyperkalemia and edema, suggesting potential benefits for patients with advanced CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Tuttle, KR., Levin, A., Nangaku, M., et al.[2022]

References

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

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. [2023]

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

The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]

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

Empagliflozin in Patients with Chronic Kidney Disease. [2023]

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

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial. [2023]

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

Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial. [2023]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Safety Analysis of Empagliflozin in Type 2 Diabetes Mellitus Patients with Chronic Kidney Disease versus Normal Kidney Function: A Nationwide Cohort Study in Korea. [2023]

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

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. [2022]

10. Belgium pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]