Indigotindisulfonate Sodium for Ureter Patency

Overseen By Michelle Boytim, P.hD.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Prove pharm

Disqualifiers: Chronic kidney failure, 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: 3

Duration: 1 day

116 Participants Needed

Trial Summary

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 treatment that could affect the main evaluation is not allowed, so it's best to discuss your medications with the study team.

How does the drug indigotindisulfonate sodium differ from other treatments for ureter patency?

Indigotindisulfonate sodium is a blue dye used during surgeries to help visualize the ureters, making it easier for surgeons to identify and examine the urinary tract. Unlike other treatments, it is specifically used for its coloring properties to improve visualization during procedures, but it has been associated with rare but serious side effects like cardiac arrest and allergic reactions. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a randomized, multicenter study to evaluate the efficacy and safety of two dose levels (2.5 mL and 5.0 mL) of Bludigo™ (indigotindisulfonate Sodium Injection, USP) 0.8% when used as an aid in the determination of ureteral patency. Subjects scheduled for a surgical procedure in which the patency of the ureter must be assessed by cystoscopy following the procedure, age 18 to 85 years inclusive, will be screened for participation. Screening will occur within 30 days before study drug administration (Day of Surgery). After signing the informed consent, review of inclusion and exclusion criteria will be performed, the collection of concomitant medications, medical history, physical examination, baseline laboratory testing, 12-lead ECG, and vital sign measurements will be completed during the screening visit. On the day of surgery (Day 1) subjects will be evaluated for eligibility for randomization. Eligible subjects will be stratified by BMI (\<30.0 kg/m2or ≥ 30.0 kg/m2) and randomized in a 1:1 ratio to receive a dose of either Bludigo™ high dose (5.0 mL) or Bludigo™ low dose (2.5 mL). Each randomized subject will serve as his/her own control (i.e., intra-patient controlled) by receiving a dose of normal saline prior to receiving the randomized Bludigo™ dose. All treated subjects will have a follow-up visit 7 to 30 days (± 2 days) after the procedure. A final telephone follow-up call will occur on Day 30 (± 2 days) in subjects who have the follow-up visit before Day 28. Safety assessments will include monitoring of AEs during and post the procedure, clinical laboratory tests, 12-Lead ECG, and vital sign measurements.

Eligibility Criteria

Adults aged 18-85 needing ureter patency assessment during surgery can join. Excluded are those with severe kidney failure, major systemic diseases, expected non-compliance, life expectancy under 6 months, pregnancy, breastfeeding, dye allergies or substance abuse within the last 6 months.

Inclusion Criteria

Subjects who signed a written IRB approved, informed consent form

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

Exclusion Criteria

Subjects, as assessed by the Investigator, with conditions/concomitant diseases precluding their safe participation in this study (e.g. major systemic diseases)

Subject is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol

I have advanced kidney failure or only one kidney.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either a high dose (5.0 mL) or low dose (2.5 mL) of Bludigo™ on the day of surgery to assess ureteral patency

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events, ECG, and vital signs

4 weeks

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

Treatment Details

Interventions

• Indigotindisulfonate Sodium Injection, USP

Trial Overview The trial tests two doses of Bludigo™ (2.5 mL and 5.0 mL) against saline to check for ureter blockages during surgery. Participants serve as their own controls by getting saline before Bludigo™ and are randomly assigned to a dose level based on BMI.

Participant Groups

Group I: Low Dose Experimental Treatment 2 Interventions

58 subjects randomly treated with 2.5 mL of drug

Group II: High Dose Experimental Treatment 2 Interventions

58 subjects randomly treated with 5 mL of drug

Group III: Saline Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Prove pharm

Lead Sponsor

Trials

5

Recruited

330+

Findings from Research

Sodium fluorescein, administered intravenously in doses of 0.25 to 1.0 mL, provides excellent visualization of ureteral jets during cystoscopy, making it a viable alternative to the previously used indigotindisulfonate sodium.

While sodium fluorescein is effective, one patient experienced transient yellowing of the sclera and palms, indicating a potential side effect, but overall it is considered a safe option for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium fluorescein use during intraoperative cystoscopy. Doyle, PJ., Lipetskaia, L., Duecy, E., et al.[2022]

Using 50% dextrose as a distension medium during cystoscopy allows for clear visualization of ureteric jets in all patients, unlike previous coloring agents that may not always provide consistent results.

The use of 50% dextrose does not interfere with the visualization of other bladder structures, making it a safe and effective alternative to indigotindisulfonate sodium for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of 50% Dextrose as the Distension Medium During Cystoscopy for Visualization of Ureteric Jets. Narasimhulu, DM., Prabakar, C., Tang, N., et al.[2021]

Indigo carmine, a blue dye commonly used in urologic and gynecologic procedures, is generally considered safe but can lead to serious adverse effects, as demonstrated in a case report.

In this case, a patient experienced hypotension, cardiac arrest, and cerebral ischemia following the administration of indigo carmine during a total laparoscopic hysterectomy, highlighting the need for caution even with routine interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac arrest from intravenous indigo carmine during laparoscopic surgery -A case report-. Lee, WJ., Jang, HS.[2021]

Indigo carmine, typically regarded as a safe dye for urinary tract examination, was associated with a severe anaphylactoid reaction and cardiac arrest in a patient after intravenous administration.

This case highlights the potential for serious allergic reactions to indigo carmine, emphasizing the need for caution and monitoring when using this agent in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening anaphylactoid reaction associated with indigo carmine intravenous injection. Gousse, AE., Safir, MH., Madjar, S., et al.[2019]

In a study of 303 women undergoing urogynecological surgery, the use of 10% dextrose in sterile water (D10) for cystoscopy was associated with a significantly higher rate of postoperative urinary tract infections (UTIs) compared to normal saline, with rates of 47.8% versus 25.9%, respectively.

Despite the increased UTI risk with D10, there were no significant differences in the rates of ureteral or lower urinary tract injuries between the D10 and normal saline groups, indicating that while D10 may help confirm ureteral patency, it poses a safety concern regarding infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing ureteral patency using 10% dextrose cystoscopy fluid: evaluation of urinary tract infection rates. Siff, LN., Unger, CA., Jelovsek, JE., et al.[2017]

References

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

Sodium fluorescein use during intraoperative cystoscopy. [2022]

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

Use of 50% Dextrose as the Distension Medium During Cystoscopy for Visualization of Ureteric Jets. [2021]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Cardiac arrest from intravenous indigo carmine during laparoscopic surgery -A case report-. [2021]

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

Life-threatening anaphylactoid reaction associated with indigo carmine intravenous injection. [2019]

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

Assessing ureteral patency using 10% dextrose cystoscopy fluid: evaluation of urinary tract infection rates. [2017]