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

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

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

Study Overview

• Status: Completed
• Conditions: Ureter Injury
• Intervention / Treatment: Drug: 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium 0.8%; Drug: Saline spray

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Adult and Pediatric Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgeon Urine Jet Conspicuity Score	The urine jet conspicuity score provided by the surgeon 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
Concordance of Conspicuity Scores	Concordance of conspicuity scores between the surgeons' assessments and the blinded central reviewer assessments. If the difference between raters in conspicuity score was within ±1 (ie, the difference ranged from 1 to +1, inclusive), the scores were considered to agree. The urine jet conspicuity score 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 Min
Conspicuity Score Difference Between the Indigo Carmine High Dose and Indigo Carmine Low Dose by Central Review Process	Exploratory analysis of the urine jet conspicuity score difference between the indigo carmine high dose and indigo carmine low dose by central review Process 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
Conspicuity Score Difference Between the Indigo Carmine High Dose and Indigo Carmine Low Dose as Assessed by Surgeons Who Were Blinded to the Dose of Indigo Carmine	Exploratory analysis of conspicuity score difference between the indigo carmine high dose and indigo carmine low dose as assessed by surgeons who were blinded to the dose of indigo carmine The urine jet conspicuity score 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

Collaborators and Investigators

• Sponsor: Prove pharm
• Investigators: Study Director: Todd Koch, Prove pharm

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 13, 2020
• Primary Completion (ACTUAL): June 3, 2021
• Study Completion (ACTUAL): June 3, 2021

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (ACTUAL): January 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: PVP-19IC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No