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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIGH DOSE | Experimental | 48 subjects randomly treated with 5 mL of drug |
|
| LOW DOSE | Experimental | 48 subjects randomly treated with 2.5 mL of drug |
|
| Saline | Placebo Comparator | 96 subjects treated with 5 ml of saline than crossover to treatment arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3,3'-Dioxo-2,2'-bisindolylidene-5,5'-disulfonate disodium 0.8% | Drug | Experimental contrast dye that is commonly used as a visualization aid in pelvic and abdominal surgeries and for various diagnostic procedures in medical practice. |
| 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.
| 10 minutes |
| 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. |
| 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.
| 10 Minutes |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Todd Koch | Prove pharm | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Adult and Pediatric Urology | Omaha | Nebraska | 68114 | United States |
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This was a crossover study where each subject served as their own control, so each subject received the control (saline solution) was evaluated for the endpoints and then received either the high or low dose based on their randomization assignment. So the total number of participants were 121 although each participant provided data for one of the active groups and the saline group.
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| ID | Title | Description |
|---|---|---|
| FG000 | SALINE Then HIGH DOSE | Approximately 48 subjects treated with 5 ml of saline than crossover to be treated with 5 mL of 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. Saline solution: Placebo |
| FG001 | SALINE Then LOW DOSE | Approximately 48 subjects treated with 5 ml of saline than crossover to be treated with 2.5 mL of 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. Saline solution: Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Population presented is the Safety Analysis Set, while the population presented in the Participant Flow was the all randomized population
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| ID | Title | Description |
|---|---|---|
| BG000 | SALINE Then HIGH DOSE | Approximately 48 subjects treated with 5 ml of saline than crossover to be treated with 5 mL of 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. Saline solution: Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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.
| The efficacy analysis set, also referred to as the modified intent-to-treat (mITT) analysis set, included all subjects in the safety analysis set who had a surgical procedure to assess ureteral patency, who received both study drugs (saline and indigo carmine), and a video approximately 10 minutes in length was available after each treatment. | Posted | Mean | Standard Deviation | score on a scale | 10 minutes |
|
Saline group: AEs collected from the time of saline administration until the beginning of indigo carmine administration (approximately 10 minutes) IC groups AEs collected from the start of IC administration until 30 (+/- 2) days post surgery
AEs were collected through non leading questioning of participants as well as via scheduled post treatment evaluation of clinical laboratories, physical exam, vital signs and EKGs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HIGH DOSE | Approximately 48 subjects randomly treated with 5 mL of 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. Saline solution: Placebo |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia aspiration (Aspiration pneumonia) | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director of Clinical Operations | Provepharm, Inc. | 6106018605 | todd.koch@provepharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: Original protocol | Jul 1, 2019 | Oct 6, 2022 | Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Administrative change #1 | Oct 18, 2019 | Oct 6, 2022 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment #1 | Dec 10, 2019 | Oct 6, 2022 | Prot_002.pdf |
| Prot | Yes | No | No | Study Protocol: Clarification Letter #1 | Jun 23, 2020 | Oct 6, 2022 | Prot_003.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment #2 | Sep 2, 2020 | Oct 6, 2022 | Prot_004.pdf |
| Prot | Yes | No | No | Study Protocol: Clarification Letter #2 | Dec 18, 2020 | Oct 6, 2022 | Prot_005.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 26, 2021 | Oct 6, 2022 | SAP_006.pdf |
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| Saline spray | Drug | Placebo |
|
| 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."
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 |
| 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.
| 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.
| 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.
| 10 Minutes |
| Withdrawal by Subject |
|
| Planned procedure not performed after randomization, study drug not administered |
|
| BG001 | SALINE Then LOW DOSE | Approximately 48 subjects treated with 5 ml of saline than crossover to be treated with 2.5 mL of 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. Saline solution: Placebo |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | LOW DOSE | Approximately 48 subjects randomly treated with 2.5 mL of 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. Saline solution: Placebo |
| OG002 | Saline | Approximately 96 subjects treated with 5 ml of saline than crossover to treatment arm Saline solution: Placebo |
|
|
|
| Secondary | 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. | The efficacy analysis set, also referred to as the modified intent-to-treat (mITT) analysis set, included all subjects in the safety analysis set who had a surgical procedure to assess ureteral patency, who received both study drugs (saline and indigo carmine), and a video approximately 10 minutes in length was available after each treatment. | Posted | Count of Participants | Participants | 10 Minutes |
|
|
|
|
| Secondary | 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."
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. | The efficacy analysis set, also referred to as the modified intent-to-treat (mITT) analysis set, included all subjects in the safety analysis set who had a surgical procedure to assess ureteral patency, who received both study drugs (saline and indigo carmine), and a video approximately 10 minutes in length was available after each treatment. | Posted | Count of Participants | Participants | 10 Minutes |
|
|
|
|
| Secondary | Time to Visualization | Time to visualization (minutes) of blue color in the ureteral jets flow following indigo carmine treatment | The efficacy analysis set, also referred to as the modified intent-to-treat (mITT) analysis set, included all subjects in the safety analysis set who had a surgical procedure to assess ureteral patency, who received both study drugs (saline and indigo carmine), and a video approximately 10 minutes in length was available after each treatment. | Posted | Median | 95% Confidence Interval | Minutes | 10 Minutes |
|
|
|
|
| Other Pre-specified | Surgeon Urine Jet Conspicuity Score | The urine jet conspicuity score provided by the surgeon as assessed by the following 5-point ordinal scale.
| The efficacy analysis set, also referred to as the modified intent-to-treat (mITT) analysis set, included all subjects in the safety analysis set who had a surgical procedure to assess ureteral patency, who received both study drugs (saline and indigo carmine), and a video approximately 10 minutes in length was available after each treatment (subjects with missing data excluded). | Posted | Mean | Standard Deviation | score on a scale | 10 Minutes |
|
|
|
|
| Other Pre-specified | 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.
| mITT Analysis Set; Subjects Without Missing Surgeon or Central Assessment Data | Posted | Count of Participants | Participants | 10 Min |
|
|
|
|
| Other Pre-specified | 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.
| mITT Analysis Set | Posted | Mean | Standard Deviation | score on a scale | 10 minutes |
|
|
|
|
| Other Pre-specified | 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.
| mITT population | Posted | Mean | Standard Deviation | score on a scale | 10 Minutes |
|
|
|
|
| 0 |
| 60 |
| 1 |
| 60 |
| 14 |
| 60 |
| EG001 | LOW DOSE | Approximately 48 subjects randomly treated with 2.5 mL of 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. Saline solution: Placebo | 0 | 58 | 3 | 58 | 14 | 58 |
| EG002 | Saline | Approximately 96 subjects treated with 5 ml of saline than crossover to treatment arm Saline solution: Placebo | 0 | 118 | 0 | 118 | 0 | 118 |
| Pulmonary embolism (Bilateral PE) | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Deep vein thrombosis (Left iliac DVT) | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
|
| Atrioventricular block complete | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
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| Percentage of Responders |
| 87.2 |
| 2-Sided |
| 95 |
| 77.7 |
| 96.8 |
Missing data imputed as non-responder |
| Other |
| 80.9 |
| 2-Sided |
| 95 |
| 67.5 |
| 89.6 |
| Other |
| 5.93 |
| 2-Sided |
| 95 |
| 5.12 |
| 7.00 |
| Other |
| Odds Ratio (OR) |
| 15.730 |
| 2-Sided |
| 95 |
| 7.199 |
| 34.369 |
| Superiority |
| Right ureter |
|
| Percentage of Agreement |
| 88.4 |
| 2-Sided |
| Other |
| Left Ureter | Percentage of Agreement | 76.1 | 2-Sided | Other |
| Right Ureter | Percentage of Agreement | 95.6 | 2-Sided | Other |
| Right Ureter | Percentage of Agreement | 86.0 | 2-Sided | Other |
| Right Ureter | Percentage of Agreement | 71.6 | 2-Sided | Other |