3,3'-Dioxo-2,2'-Bisindolylidene-5,5'-Disulfonate Disodium 0.8% Solution as an Aid for Ureteral Patency

Study Overview
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Brief Summary
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To determine whether the use of 3,3'-Dioxo-2,2'-Bisindolylidene-5,5'-Disulfonate Disodium 0.8% Solution for injection provides a visualization advantage compared to saline when used as an aid in the determination of ureteral patency

Detailed Description
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This is an open-label, randomized, multicenter study to evaluate the efficacy, safety, and pharmacokinetics of two doses (2.5 mL and 5.0 mL) of 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium solution for injection when used as an aid in the determination of ureteral patency. Study will enroll up to 116 subjects from approximately 10 study centers in the United States.

Official Title
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An Open-Label Study of Two Different Doses of 3,3'-Dioxo-2,2'-Bisindolylidene-5,5'-Disulfonate Disodium 0.8% Solution When Used as an Aid for Ureteral Patency

Conditions
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Ureter Injury

Intervention / Treatment
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* Drug: 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium 0.8%
* Drug: Saline spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects between ≥ 18 and ≤ 85 years old. Subjects who signed written, IRB approved, informed consent form. Subjects scheduled for urological or gynecological surgical procedures in which the patency of the ureter must be assessed by the surgeon during the procedure Exclusion Criteria: Subjects with stage 4 or 5 Chronic Kidney Failure as evidenced by a GFR <30 mL/min/1.73m2 (using the MDRD) or need for dialysis in the near future, or having only 1 kidney. Subjects with known severe hypersensitivity reactions to IC or other dyes including contrast agents. Known history of drug or alcohol abuse within 6 months prior to the time of screening visit. Subjects, as assessed by the Investigator, with conditions/concomitant diseases precluding their safe participation in this study (e.g. major systemic diseases). Unable to meet specific protocol requirements (e.g., scheduled visits) or subject is uncooperative or has a condition that could lead to non-compliance with the study procedures. 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; Subjects with life expectancy < 6 months; Requirement for concomitant treatment that could bias primary evaluation. Subjects who are pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIGH DOSE<br>48 subjects randomly treated with 5 mL of drug | Drug: 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium 0.8%<br>* Experimental contrast dye that is commonly used as a visualization aid in pelvic and abdominal surgeries and for various diagnostic procedures in medical practice.<br>Drug: Saline spray<br>* Placebo<br>|
| Experimental: LOW DOSE<br>48 subjects randomly treated with 2.5 mL of drug | Drug: 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium 0.8%<br>* Experimental contrast dye that is commonly used as a visualization aid in pelvic and abdominal surgeries and for various diagnostic procedures in medical practice.<br>Drug: Saline spray<br>* Placebo<br>|
| Placebo Comparator: Saline<br>96 subjects treated with 5 ml of saline than crossover to treatment arm | Drug: Saline spray<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Jet Conspicuity Score | The urine jet conspicuity score provided by the blinded central review process as assessed by the following 5-point ordinal scale. = No jet observed = Weak jet, little color contrast = Color contrast or significant jet flow = Strong jet flow with good color contrast = Strong jet flow with striking contrast in color | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders | A subject was a responder when there was ≥1-point improvement in the urine jet conspicuity scores following the indigo carmine versus saline treatment (indigo carmine - saline ≥1) and the conspicuity score following the indigo carmine treatment was 3, 4, or 5. The responder criteria were assessed separately for each ureter for each subject based on the blinded central reviewer's conspicuity score. | 10 Minutes | 
| Physician Satisfaction Agreement Scale | After the completion of the procedure, the surgeon rated the experience of using indigo carmine for each subject using the 5-point PSAS, in which: Compared to the use of saline treatment, my ability to assess ureteral patency was improved after the addition of indigo carmine. = Strongly Agree = Agree = Neither Agree nor Disagree = Disagree = Strongly Disagree The surgeon was considered satisfied with the indigo carmine treatment if his/her rating was either a 1 (strongly agree) or a 2 (agree); otherwise, the surgeon was considered unsatisfied with the indigo carmine treatment. | 10 Minutes | 
| Time to Visualization | Time to visualization (minutes) of blue color in the ureteral jets flow following indigo carmine treatment | 10 Minutes |