Indigotindisulfonate Sodium for Kidney Failure

Overseen By Michelle Boytim, P.hD.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Prove pharm

Disqualifiers: Dialysis, Hypersensitivity, Drug abuse, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label, randomized, multicenter study to evaluate the efficacy and safety of two dose levels (2.5 mL and 5.0 mL) of Indigotindisulfonate Sodium Injection, USP 0.8% when used as an aid in the determination of ureteral patency in patients with different degrees of renal impairment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any required treatment that could affect the main evaluation might be a concern, so it's best to discuss your specific medications with the study team.

What makes the drug Indigotindisulfonate Sodium unique for treating kidney failure?

Indigotindisulfonate Sodium is unique because it is used as a dye in medical imaging to help visualize kidney function, which is different from other treatments that focus on directly treating kidney failure. This drug's role in enhancing imaging can aid in better diagnosis and management of kidney conditions. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 18-85 with varying degrees of kidney function, from normal to severe impairment. They must be scheduled for surgery where ureter health will be checked and have given written consent. People with recent acute illness or unstable renal insufficiency are excluded.

Inclusion Criteria

I am between 18 and 85 years old.

I am scheduled for surgery that requires checking the health of my ureter afterwards.

My kidneys are healthy and I am in good overall health.

Exclusion Criteria

Subjects who are pregnant or breast-feeding

My kidney function is very low, I might need dialysis soon, or I have only one kidney.

Subjects with known severe hypersensitivity reactions to Bludigo™ or other dyes, including contrast dyes

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Baseline evaluation including eGFR determination, medical history, and baseline laboratory testing

1-2 days

1 visit (in-person)

Treatment

Participants receive either a high or low dose of Bludigo™ following a saline injection, with onsite observation for 24 hours post-dose

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up visit and a final telephone call

7 to 30 days

1 visit (in-person), 1 call (telephone)

Treatment Details

Interventions

• Indigotindisulfonate Sodium Injection, USP

Trial Overview The study tests two doses (2.5 mL and 5.0 mL) of Indigotindisulfonate Sodium Injection, USP 0.8%, to see how well it helps determine if the tubes connecting the kidneys and bladder (ureters) are open in patients with different levels of kidney function.

Participant Groups

Group I: Low Dose Experimental Treatment 2 Interventions

24 subjects randomly treated with 2.5 mL of drug

Group II: High Dose Experimental Treatment 2 Interventions

24 subjects randomly treated with 5 mL of drug

Group III: Saline Placebo Group 1 Intervention

48 subjects treated with 5 ml of saline then crossover to treatment arm

Indigotindisulfonate Sodium Injection, USP is already approved in United States for the following indications:

Approved in United States as Bludigo for:

• Visualization aid in the cystoscopic assessment of the integrity of the ureters following urological and gynecological open, robotic, or endoscopic surgical procedures

Who Is Running the Clinical Trial?

Prove pharm

Lead Sponsor

Trials

5

Recruited

330+

Findings from Research

Cisplatin-induced acute kidney injury (AKI) leads to significantly increased levels of indoxyl sulfate (IS) in the serum and kidneys, which correlates with the down-regulation of renal organic ion transporters (rOAT1, rOAT3, and rMATE1).

The administration of AST-120, an oral charcoal adsorbent, partially reverses the effects of cisplatin by restoring the function and expression of these transporters, suggesting a potential therapeutic approach to mitigate the effects of AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of renal organic ion transporters in cisplatin-induced acute kidney injury and uremia in rats. Morisaki, T., Matsuzaki, T., Yokoo, K., et al.[2021]

Adding 2% poly-β-cyclodextrins (PCDs) to the dialysate during hemodialysis significantly improved the clearance of indoxyl sulphate (IS) in uremic rats, achieving about a twofold increase compared to conventional hemodialysis.

Increasing the concentration of PCDs to 4% did not further enhance IS clearance, indicating that 2% PCD is the optimal concentration for improving the removal of this uremic toxin in the studied model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased clearance of indoxyl sulphate in renal failure rats with the addition of water-soluble poly-β-cyclodextrin to the dialysate. Liu, S., Jia, L., Xiao, J., et al.[2023]

Indoxyl sulfate (IS) significantly promotes collagen synthesis and myocyte hypertrophy in cardiac cells, indicating its role in adverse cardiac remodeling, with increases of 145.7% and 134.5% respectively compared to control.

IS activates pro-inflammatory pathways in cardiac cells, specifically through the p38 MAPK and NFkappaB pathways, suggesting that targeting IS or these pathways could be a new treatment strategy for patients with chronic kidney disease and chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Lekawanvijit, S., Adrahtas, A., Kelly, DJ., et al.[2013]

Indoxyl sulfate (IS) administration in both normal and chronic renal failure (CRF) rats led to decreased antioxidative capacity in the kidneys, as evidenced by reduced superoxide scavenging activity and lower levels of superoxide dismutase (SOD).

The study demonstrated that IS not only increased levels of uremic toxins and serum creatinine but also impaired the kidney's redox status, suggesting that IS contributes to nephrotoxicity by disrupting antioxidative systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Owada, S., Goto, S., Bannai, K., et al.[2015]

Indoxyl sulphate, a toxic substance that builds up in chronic renal failure, is primarily eliminated from the plasma through the kidneys, with its uptake being mediated by an organic anion transport system.

In chronic renal failure rats, the elimination rate of indoxyl sulphate from plasma is significantly lower compared to normal rats, indicating impaired kidney function affects the clearance of this harmful toxin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats. Deguchi, T., Nakamura, M., Tsutsumi, Y., et al.[2014]

References

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

Regulation of renal organic ion transporters in cisplatin-induced acute kidney injury and uremia in rats. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Increased clearance of indoxyl sulphate in renal failure rats with the addition of water-soluble poly-β-cyclodextrin to the dialysate. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats. [2014]