An Open-Label, Randomized, Parallel Group Study to Investigate the Influence of Renal Impairment on the Efficacy and Safety of Two Doses of Bludigo™ When Used as an Aid in the Determination of Ureteral Patency
概览
- 阶段
- 4 期
- 干预措施
- Saline Injection 0.9%
- 疾病 / 适应症
- Ureter Injury
- 发起方
- Prove pharm
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Paired sample difference (Bludigo - Saline) in urine jet conspicuity score.
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
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 Injection, USP 0.8% when used as an aid in the determination of ureteral patency in patients with different degrees of renal impairment.
详细描述
An estimated glomerular filtration rate (eGFR) at baseline will be determined using the Modification of Diet in Renal Disease (MDRD) and standardized by using individual's body surface area as described in the FDA's Renal Impairment guidance. Qualified subjects/patients will be stratified into 4 cohorts based on their eGFR at baseline: patients with normal renal function (eGFR ≥ 90 mL/min), patients with mild (eGFR 60-89 mL/min), moderate (eGFR 30-59 mL/min) and severe (eGFR 15-29 mL/min) renal impairment. Up to ten study centers in the United States will enroll up to approximately 12 subjects per cohort (48 subjects in total) 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 covering the full renal function range from normal, mild, moderate, and severe renal impairment. For each subject/patient the study will consist of a screening period (Day -30 to Day -2), a baseline evaluation (Day -1 to Day 1) and a single treatment period (Day 1) with an onsite observation period of 24 hours post-dose. 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 cohort 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). All randomized subjects will serve as his/her own control (i.e., intra-patient controlled) for efficacy by receiving a dose of normal saline prior to receiving the randomized Bludigo™ dose. The surgeon will be blinded to the Bludigo™ dose a subject receives. Time of injection of saline and Bludigo™ will be captured. 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.
研究者
入排标准
入选标准
- •Subjects between ≥ 18 and ≤ 85 years old
- •Subjects who signed a written IRB approved, informed consent form
- •Subjects scheduled for a surgical procedure in which the patency of the ureter must be assessed by cystoscopy following the procedure.
- •An estimated glomerular filtration rate (eGFR) at baseline will be determined using the Modification of Diet in Renal Disease formula (MDRD) and standardized by using individual's body surface area.
- •Subject's renal function will be defined based on the following criteria:
- •Normal subjects: eGFR of ≥90 mL/min
- •Mild renal impairment: eGFR 60 to 89 mL/min
- •Moderate renal impairment: eGFR 30 to 59 mL/min
- •Severe renal impairment: eGFR 15 to 29 mL/min
- •Subjects with normal renal function that are judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests performed at the Screening Visit and/or prior to administration of study drug.
排除标准
- •Subjects with eGFR \<15 mL/min or expected need for dialysis in the near future, or having only 1 kidney
- •Subjects with known severe hypersensitivity reactions to Bludigo™ or other dyes, including contrast dyes
- •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
研究组 & 干预措施
Saline
48 subjects treated with 5 ml of saline then crossover to treatment arm
干预措施: Saline Injection 0.9%
High Dose
24 subjects randomly treated with 5 mL of drug
干预措施: Saline Injection 0.9%
High Dose
24 subjects randomly treated with 5 mL of drug
干预措施: Indigotindisulfonate sodium 0.8%
Low Dose
24 subjects randomly treated with 2.5 mL of drug
干预措施: Saline Injection 0.9%
Low Dose
24 subjects randomly treated with 2.5 mL of drug
干预措施: Indigotindisulfonate sodium 0.8%
结局指标
主要结局
Paired sample difference (Bludigo - Saline) in urine jet conspicuity score.
时间窗: 10 to 15 minutes post study drug administration
Visualization will be measured by a conspicuity scale designed to provide an objective tool applicable to the visualization of the urinary flow from the ureteral orifices when determining ureter patency. The conspicuity of the urine flow from the ureteral orifices is defined using the 5-point conspicuity score as follows: 1. = No jet observed 2. = Weak jet, little color contrast 3. = Color contrast or significant jet flow 4. = Strong jet flow with good color contrast 5. = Strong jet flow with striking contrast in color Paired sample difference (Bludigo™-Saline) in conspicuity score (PSDCS). PSDCS will be calculated for each ureter (left or right) for each subject from each reviewer.
Responders to Bludigo
时间窗: 10 to 15 minutes post study drug administration
Visualization will be measured by a conspicuity scale designed to provide an objective tool applicable to the visualization of the urinary flow from the ureteral orifices when determining ureter patency. The conspicuity of the urine flow from the ureteral orifices is defined using the 5-point conspicuity score as follows: 1. = No jet observed 2. = Weak jet, little color contrast 3. = Color contrast or significant jet flow 4. = Strong jet flow with good color contrast 5. = Strong jet flow with striking contrast in color A subject is considered a responder to Bludigo™ if there is \>=1 point improvement in the conspicuity score following the Bludigo™- treatment vs the saline treatment and the conspicuity score for the Bludigo™ treatment must be (3, 4, or 5). The responder criteria will be assessed separately for each ureter (left or right) from each reviewer.
次要结局
- Changes in clinical safety laboratory values(30 days post study drug administration)
- Incidence of adverse events and serious adverse events.(30 days post study drug administration)
- Changes in heart rate by dose group and Renal Impairment Cohort(30 days post study drug administration)
- Changes in vital signs post treatment(30 days post study drug administration)
- Changes in ECG post treatment(30 days post study drug administration)
- Changes in pulse oximetry by dose group and Renal Impairment Cohort(30 days post study drug administration)
- Changes in blood pressure by dose group and Renal Impairment Cohort(30 days post study drug administration)
- Time to visualization(10 to 15 minutes post study drug administration)
- Physician Satisfaction(10 to 15 minutes post study drug administration)