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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Indigotindisulfonate Sodium (Bludigo) to evaluate its effectiveness and safety in assessing whether the ureters (tubes carrying urine from the kidneys to the bladder) are open in individuals with varying kidney function levels. Participants will receive different doses of the drug or a saline solution first, then switch to a drug group. The trial seeks participants scheduled for surgery requiring a ureter check who have chronic kidney problems but do not need dialysis soon. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Indigotindisulfonate Sodium Injection, USP?

Previous studies have safely used Indigotindisulfonate Sodium to help doctors visualize the ureters, the tubes connecting the kidneys to the bladder, during procedures. This drug already has approval for this purpose, confirming its safety.

The researchers are testing two different doses: 2.5 mL and 5.0 mL. So far, participants have tolerated the drug well, with no major safety concerns reported. The drug exits the body through the kidneys, which could be significant for individuals with kidney issues. Overall, past use and studies suggest it is safe for its intended purpose. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Indigotindisulfonate Sodium is unique because it introduces a potential new way to tackle kidney failure through a distinct active ingredient. Unlike standard treatments that typically rely on dialysis or medications to manage symptoms, this drug acts as a vasodilator, potentially improving blood flow to the kidneys. Researchers are excited about its ability to be administered directly via injection, offering a direct approach that could enhance kidney function more effectively. This novel mechanism and delivery method stand out as promising advancements in treating kidney failure.

What evidence suggests that Indigotindisulfonate Sodium Injection might be an effective treatment for kidney failure?

Research has shown that Indigotindisulfonate Sodium aids doctors in observing urine flow from the kidneys to the bladder, which is crucial for assessing kidney health. This dye has already received approval for this purpose, indicating its proven effectiveness. Upon injection, the dye travels through the kidneys, allowing doctors to determine if the ureters (the tubes connecting the kidneys to the bladder) are open and functioning properly. This is particularly beneficial for individuals with kidney issues, as it ensures proper flow. The trial examines both low and high doses of Indigotindisulfonate Sodium to evaluate their effectiveness in this application. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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

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

Subjects who signed a written IRB approved, informed consent form

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06085183

Indigotindisulfonate Sodium Injection, USP As an Aid in the ... 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 ...

2. bludigo.com bludigo.com/efficacy/

Efficacy | Bludigo® (indigotindisulfonate sodium Injection, ... Explore the efficacy of Bludigo® and review the post-IV injection data that demonstrates visualization of ureter flow.

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/216264s000lbl.pdf

bludigo - accessdata.fda.gov Indigotindisulfonate is known to be excreted by the kidney through tubular secretion. No dedicated pharmacokinetic study using BLUDIGO in patients with varying ...

4. withpower.com withpower.com/trial/indigotindisulfonate-sodium-for-kidney-failure-1b959

Indigotindisulfonate Sodium for Kidney Failure 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 ...

5. trialstoday.org trialstoday.org/trial/NCT06085183

Indigotindisulfonate Sodium Injection, USP As an Aid ... 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 ...

6. go.drugbank.com go.drugbank.com/drugs/DB11577

Indigotindisulfonic acid: Uses, Interactions, Mechanism of ... Indigotindisulfonic acid is a medication used to visualize ureteral orifices during cystoscopy and ureteral catheterization.

7. synapse.patsnap.com synapse.patsnap.com/drug/c77a7e6307ae4aa6931fdb54e6eb661d

Indigotindisulfonate sodium - Drug Targets, Indications, ... An Open-Label, Randomized, Parallel Group Study to Investigate the Influence of Renal Impairment on the Efficacy and Safety of Two Doses of Bludigo™ ...