Canagliflozin for Chronic Kidney Disease

(SIP-AKiD Trial)

Recruiting at 1 trial location

Overseen By Norka Rios

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: SGLT-2 inhibitors

Disqualifiers: Type 1 diabetes, Liver disease, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests canagliflozin, a medication, to evaluate its effectiveness for people with chronic kidney disease (CKD). Researchers aim to determine if it can reduce protein in the urine, a common issue for those with CKD, and whether different doses of the drug are more effective or equally safe. The trial seeks adults with serious kidney issues who are either not yet on dialysis or have been on hemodialysis for at least three months. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like digoxin, phenobarbital, phenytoin, rifampin, or ritonavir if they cannot be safely discontinued. If you are on these medications, you may need to stop them to participate.

What is the safety track record for canagliflozin?

Studies have shown that canagliflozin can significantly reduce the risk of kidney failure in people with type 2 diabetes and chronic kidney disease. However, some safety concerns exist. Research indicates that patients with kidney issues using canagliflozin might face a higher risk of sudden kidney problems, where kidneys could stop functioning properly without warning.

Additionally, individuals with kidney problems may experience low blood pressure when taking canagliflozin. Despite these risks, previous findings suggest that canagliflozin can reduce both serious and minor kidney-related side effects in some patients.

Overall, while safety concerns exist, canagliflozin has demonstrated benefits for kidney health in certain cases. Individuals should discuss these factors with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Canagliflozin is unique because it works by inhibiting the sodium-glucose co-transporter 2 (SGLT2) in the kidneys, which not only helps control blood sugar levels but also provides kidney protection. Unlike traditional treatments for chronic kidney disease, which often include blood pressure medications and ACE inhibitors, canagliflozin offers a dual benefit by also addressing cardiovascular risks. Researchers are excited about canagliflozin because it has the potential to slow kidney damage progression while simultaneously reducing heart-related issues, making it a promising option for comprehensive disease management.

What is the effectiveness track record for canagliflozin in treating chronic kidney disease?

Research shows that canagliflozin effectively aids people with type 2 diabetes and chronic kidney disease (CKD). Studies have found that patients taking canagliflozin experienced a 30% lower risk of serious kidney problems, such as kidney failure or a significant increase in a waste product in the blood, compared to those not taking the drug. Additionally, canagliflozin significantly reduced major heart-related issues in these patients. These benefits occur regardless of blood sugar levels, suggesting that canagliflozin may directly protect the kidneys and heart. The evidence strongly supports canagliflozin's effectiveness in treating kidney problems in patients with diabetes, and researchers are now studying it further in those with more advanced CKD. ^{6 7 8 9 10}

Who Is on the Research Team?

Thomas Mavrakanas, MD

Principal Investigator

Research Institute of the McGill University Health Center

Are You a Good Fit for This Trial?

Adults with advanced chronic kidney disease (CKD) can join this trial. For one part, they need an eGFR <30 ml/min/1.73m2 and high urine albumin but not on dialysis. Another part is for those on hemodialysis for at least 3 months without much remaining kidney function. People under 18, with type 1 diabetes, recent SGLT-2 inhibitor use, severe liver disease, certain medication use that can't be stopped, or who are pregnant/breastfeeding cannot participate.

Inclusion Criteria

My kidney function is low, with an eGFR under 30.

I have been on hemodialysis for at least 3 months.

I produce less than 250 ml of urine in 24 hours.

Exclusion Criteria

currently breastfeeding

I am under 18 years old.

I frequently have severe genital or urinary infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Patients with eGFR<30 ml/min/1.73m2 and UACR>200 mg/g not receiving dialysis will receive canagliflozin 100 mg po daily

12 weeks

Treatment Phase 2

For participants who have tolerated the drug, canagliflozin will be increased to 300 mg po daily

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Substudy 2 Treatment

Adult patients on HD for at least 3 months without significant residual renal function will receive canagliflozin 100 mg po daily

9 days

What Are the Treatments Tested in This Trial?

Interventions

• Canagliflozin

Trial Overview The trial tests Canagliflozin's effects in CKD patients including those on hemodialysis (HD). It aims to see if the drug reduces protein in urine and has cardiovascular/kidney protection benefits as seen in less severe cases. Two doses of Canagliflozin (100 mg and 300 mg) will be compared for safety and effectiveness.

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

Approved in European Union as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction

Approved in United States as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction
• Diabetic kidney disease

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Canagliflozin, an SGLT-2 inhibitor, showed potential in improving kidney function in rats with non-diabetic chronic kidney disease (CKD) induced by adenine, significantly reducing inflammation and oxidative stress markers.

The drug did not cause any significant adverse effects, suggesting it may be safe for further investigation in human trials for CKD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. Ali, BH., Al Salam, S., Al Suleimani, Y., et al.[2020]

In a large retrospective cohort study involving over 55,000 patients with type 2 diabetes, canagliflozin was associated with a significantly lower risk of hospital admission for heart failure compared to DPP-4 inhibitors, GLP-1 receptor agonists, and sulfonylureas.

Canagliflozin showed similar risks for major cardiovascular events (like heart attacks and strokes) when compared to these other diabetes medications, indicating its safety profile in terms of cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. Patorno, E., Goldfine, AB., Schneeweiss, S., et al.[2022]

Canagliflozin, a sodium-glucose co-transporter 2 inhibitor for type 2 diabetes, can cause acute pancreatitis, a very rare side effect occurring in less than 1% of patients, as demonstrated in a case of a 50-year-old male who developed diabetic ketoacidosis after 4 days of treatment.

The case highlights the importance of monitoring for serious side effects like acute pancreatitis when prescribing canagliflozin, emphasizing the need for more detailed guidelines on patient selection for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pancreatitis in the use of canagliflozin: A rare side-effect of the novel therapy for type 2 diabetes mellitus. Srivali, N., Thongprayoon, C., Cheungpasitporn, W., et al.[2020]

Canagliflozin is effective in improving glycemic control in adults with type 2 diabetes, specifically by inhibiting SGLT2 to increase urinary glucose excretion, with a focus on patients having a baseline eGFR of 45 mL/min/1.73 m² or higher.

The safety analyses conducted during the clinical development of canagliflozin provided a comprehensive understanding of its impact on renal function, allowing for informed dosing recommendations in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization. Khurana, M., Vaidyanathan, J., Marathe, A., et al.[2022]

Canagliflozin, an SGLT-2 inhibitor introduced for type 2 diabetes, shows potential for type 1 diabetes treatment due to its insulin-independent mechanism of action.

However, it carries serious risks, including severe metabolic acidosis and euglycemic diabetic ketoacidosis, which require immediate recognition and treatment to prevent life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. Gelaye, A., Haidar, A., Kassab, C., et al.[2022]

Canagliflozin, an SGLT2 inhibitor, effectively lowers blood sugar levels and HbA1c by promoting glucose excretion in urine, with an average HbA1c reduction of 0.75% when used alongside other diabetes treatments.

While canagliflozin is generally safe, it can cause genital infections and urinary tract infections, and caution is advised for elderly patients and those with renal insufficiency, as its efficacy decreases with lower kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes]. Scheen, AJ.[2018]

Canagliflozin significantly reduces the risk of cardiovascular events and kidney outcomes in individuals with type 2 diabetes, showing a consistent relative effect across different KDIGO risk categories based on kidney function and albumin levels.

Higher KDIGO risk categories experienced greater absolute reductions in cardiovascular outcomes, suggesting that patients with more severe kidney disease may benefit more from canagliflozin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Neuen, BL., Ohkuma, T., Neal, B., et al.[2021]

Canagliflozin significantly improved glycemic control in patients with type 2 diabetes and stage 3 chronic kidney disease, reducing HbA1c levels compared to placebo after 26 weeks.

The treatment was generally well tolerated, with similar rates of adverse events compared to placebo, although there were slightly higher instances of urinary tract infections and other osmotic diuresis-related effects at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Yale, JF., Bakris, G., Cariou, B., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1811744

Canagliflozin and Renal Outcomes in Type 2 Diabetes and ... In this trial, we found that patients with type 2 diabetes and chronic kidney disease who received canagliflozin had a lower risk of the primary composite ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7261301/

Canagliflozin for the Treatment of Diabetic Kidney Disease ... Canagliflozin treatment was associated with a 30% relative risk reduction of the primary composite outcome of ESKD, doubling of serum creatinine ...

3. jnj.com jnj.com/media-center/press-releases/invokana-canagliflozin-significantly-reduced-major-cardiovascular-events-and-kidney-failure-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-in-new-credence-analysis

INVOKANA® (canagliflozin) Significantly Reduced Major ... INVOKANA® (canagliflozin) Significantly Reduced Major Cardiovascular Events and Kidney Failure in Patients with Type 2 Diabetes and Chronic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6181277/

Cardiovascular and Renal Outcomes With Canagliflozin ... The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55–0.90) and those with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02065791

NCT02065791 | Evaluation of the Effects of Canagliflozin ... The goal of this study is to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5485046/

Renal safety of canagliflozin, a sodium glucose co‐ ... The recent FDA revision to the labels for the SGLT2 inhibitors canagliflozin, dapagliflozin and empagliflozin suggests an increased risk of acute kidney injury ...

7. invokanahcp.com invokanahcp.com/

INVOKANA® (canagliflozin) Official Website HCP Patients with renal impairment using INVOKANA® for glycemic control may be more likely to experience hypotension and may be at a higher risk for acute kidney ...

8. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin

FDA strengthens kidney warnings for diabetes medicines ... The US Food and Drug Administration (FDA) has strengthened the existing warning about the risk of acute kidney injury for the type 2 diabetes medicines.

9. jnj.com jnj.com/media-center/press-releases/invokana-canagliflozin-significantly-reduces-the-risk-of-renal-failure-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-in-the-landmark-phase-3-credence-study

INVOKANA® (canagliflozin) Significantly Reduces the Risk ... INVOKANA (canagliflozin) significantly reduces the risk of renal failure in patients with type 2 diabetes and chronic kidney disease.

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34029680/

Canagliflozin and Kidney-Related Adverse Events in Type ... Canagliflozin was associated with a reduced incidence of serious and nonserious kidney-related AEs in patients with T2DM and CKD.