Empagliflozin for Chronic Kidney Disease

(SGLT2I-IN-KIDS Trial)

Overseen By Alexander J Kula, MD, MHS

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Must not be taking: SGLT2i, Immunosuppressives

Disqualifiers: Heart disease, Diabetes, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medication empagliflozin (also known as Jardiance) can benefit young people with chronic kidney disease (CKD) by improving factors linked to worsening kidney and heart health. Researchers aim to enroll 40 young participants to determine if taking this medication for three months leads to positive changes in health tests. Participants will be randomly assigned to either take empagliflozin or continue with their regular care, with regular check-ins and tests. This trial might suit young people with moderate CKD who do not have other conditions like heart disease or diabetes. As an Early Phase 1 trial, this research focuses on understanding how empagliflozin works in young people with CKD.

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 participate if you are currently using an SGLT2 inhibitor or need to adjust your blood pressure medications in the next 3 months.

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

Research has shown that empagliflozin is generally safe for people with chronic kidney disease (CKD) and type 2 diabetes. One study found no new safety issues when patients with these conditions used empagliflozin. Another study demonstrated that this treatment reduced the risk of kidney disease worsening and lowered the chance of heart-related death compared to a placebo, which contains no active medicine.

However, reports have indicated serious kidney problems, such as sudden kidney failure, in some patients using similar medications, especially those with type 2 diabetes. Consider this if thinking about joining a trial. While the results for empagliflozin are promising, discussing any potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Empagliflozin stands out because it offers a novel approach to treating chronic kidney disease by targeting the sodium-glucose co-transporter 2 (SGLT2), a mechanism not commonly addressed in standard care options like ACE inhibitors or ARBs. This mechanism helps reduce blood sugar and may also provide kidney protection, which is an exciting prospect for chronic kidney disease management. Researchers are particularly enthusiastic because empagliflozin has shown promise in not only managing glucose levels but potentially slowing kidney disease progression, offering a dual benefit that could improve patient outcomes significantly.

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

Research has shown that empagliflozin can benefit people with chronic kidney disease (CKD). Studies have found that it slows the progression of kidney disease and reduces the risk of death from heart problems compared to a placebo. In this trial, participants in the treatment arm will receive empagliflozin. The EMPA-KIDNEY trial demonstrated that it slows disease progression, even in those with low levels of the protein albumin in their urine. Additionally, empagliflozin has been linked to improved quality of life and reduced healthcare costs over time. These findings suggest that empagliflozin could protect kidney function and lower heart risks for those with CKD. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for young people with chronic kidney disease (CKD). To join, they must be eligible to start treatment and willing to take a daily pill or stick with their usual care. They'll also need to check in by phone every two weeks and visit the clinic at specific times.

Inclusion Criteria

My kidney function is moderately to severely reduced.

Exclusion Criteria

Pregnancy

Lack of clearance by primary nephrologist for participation

I am able to follow study instructions and procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin once daily for 3 months

12 weeks

Clinic visits at 4 and 8 weeks, phone calls every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests if it's possible to run a larger trial on Empagliflozin (a diabetes drug) in kids with CKD, and if taking it for 3 months improves blood, urine, and heart function. Participants are randomly chosen to either get the drug or continue regular care.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Empagliflozin 10mg daily for 3 months (n=20)

Group II: Standard of Care Active Control 1 Intervention

Participants will not take empagliflozin (n=20)

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

Approved in European Union as Jardiance for:

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

Approved in United States as Jardiance for:

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

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?

Ann & Robert H Lurie Children's Hospital of Chicago

Lead Sponsor

Trials

275

Recruited

5,182,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

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 EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[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]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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 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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204233

Empagliflozin in Patients with Chronic Kidney Disease Empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7615591/

Effects of Empagliflozin on Progression of Chronic Kidney ... Empagliflozin slowed the rate of progression of CKD among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39446272

Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the ... Empagliflozin + SoC would have a positive impact on patients with CKD by slowing CKD progression and leading to the prevention of kidney failure ...

4. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/ckd/efficacy

CKD Efficacy | Jardiance® (empagliflozin) tablets JARDIANCE helps reduce the risk of kidney disease progression and CV death · *. Actual event rates for kidney disease progression or CV death: 16.9% (n=558/3305) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025002706

Effects of empagliflozin on quality of life and healthcare use ... In summary, 2 years of allocation to empagliflozin in EMPA-KIDNEY increased quality-of-life-adjusted survival and reduced use and cost of other healthcare ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9210861/

Safety of Empagliflozin in Patients With Type 2 Diabetes ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...

7. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(25)00222-0/fulltext

an individual participant-level meta-analysis The risk of kidney failure was reduced by 34%. Benefits were evident irrespective of the predicted size of the acute dip in eGFR and ...

8. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/payor/vital-perspectives/jardiance/clinical/guidelines/ckd

Guidelines - Chronic Kidney Disease | Jardiance Clinical Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including JARDIANCE.