Safety and Feasibility of ActivSight(tm) in the Identification of The Ureter Via Riboflavin Fluorescence

The main Objective of this study is to determine the safety and feasibility of a prototype ActivSightTM in identifying the ureter in real-time during elective laparoscopic abdominopelvic surgery after pre-surgical administration of riboflavin. This study seeks to identify the ureter only; ActivSight™ will not be used to Safety and Feasibility of ActivSightTM in the Identification of the Ureter via Riboflavin Fluorescence guide treatment or the surgical procedure. As such, this is a non-significant risk study. Riboflavin is a common dietary supplement and will be administered at dosages shown previously to be well-tolerated for migraine prophylaxis [6]. ActivSight™ is an imaging system connected to the standard laparoscopic system already existing in the OR at the site. Changes made to the commercial ActivSight™ hardware for this study introduce no significant risk

Study Overview

• Status: Withdrawn
• Conditions: Surgical Procedure, Unspecified
• Intervention / Treatment: Device: Investigational Safety and Feasibility

Detailed Description

In the 2019 publication, "A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery," by de Valk, et al. [1], the authors present the clinical need for real-time identification of the ureter during laparoscopic abdominal surgery: "Iatrogenic ureteral injury is amongst the most feared complications of lower abdominal surgery, with incidence varying from 0.5 - 1% in cancer surgery, to as high as 10% in gynecologic oncologic surgery [2-5]. Ureters are thin-walled and at risk for injury as they are poorly distinguished from surrounding retroperitoneal tissue and are usually in a collapsed state. Unrecognized ureteral damage during surgery can lead to long-term morbidity, including kidney failure." In their publication, this team proposes the use of a zwitterionic near-infrared fluorophore that could be detected in real-time via near-infrared fluorescence imaging. Activ Surgical has developed and commercialized ActivSight™, a near-infrared fluorescence detector, that combines an innovative form factor and proprietary software to deliver precise, objective, cost efficient real-time visualization of blood flow and tissue perfusion intraoperatively for laparoscope-based surgery. A small adaptor fits between any existing laparoscope and camera system and a separate light source is placed along any current commercial system to deliver objective real-time tissue perfusion and blood flow information intraoperatively. ActivSight™ received 510(k) clearance from the US FDA in 2020. According to its labelling, ActivSight™ is intended to provide real-time endoscopic fluorescence and near infrared imaging. ActivSight™ enables surgeons to visually assess blood flow and related tissue perfusion using fluorescence and near infrared imaging, and at least one of the major bile ducts (cystic duct, common bile duct or common hepatic duct) using fluorescence, all during minimally invasive surgery. In this clinical feasibility study, Activ Surgical proposes a slightly different approach from the above-referenced publication to achieve real-time ureter identification during elective laparoscopic abdominal surgery. Instead of utilizing a zwitterionic fluorophore to fluoresce the ureter, Activ Surgical is investigating a common over-the-counter water-soluble vitamin: riboflavin, also known as vitamin B2.

While typically administered as a dietary supplement, the medical literature contains many large studies of riboflavin use as prophylaxis for migraines [6]. It has also been studied and used to identify ureteral jets during cystoscopy as a method of confirming ureter patency after pelvic prolapse surgery [7-8].

Riboflavin possesses properties of fluorescence, with three strong areas of fluorescence [9] in the visible wavelength spectrum. To detect the fluorescence of riboflavin, changes were made to ActivSight™ hardware for this study; these changes are detailed herein. The main Objective of this study is to determine the safety and feasibility of a prototype ActivSightTM in identifying the ureter in real-time during elective laparoscopic abdominopelvic surgery after pre-surgical administration of riboflavin. This study seeks to identify the ureter only; ActivSight™ will not be used to guide treatment or the surgical procedure. As such, this is a non-significant risk study. Riboflavin is a common dietary supplement and will be administered at dosages shown previously to be well-tolerated for migraine prophylaxis [6]. ActivSight™ is an imaging system connected to the standard laparoscopic system already existing in the OR at the site. Changes made to the commercial ActivSight™ hardware for this study introduce no significant risk. Subjects presenting for elective laparoscopic abdominopelvic surgery (meeting the inclusion/exclusion criteria detailed below) will be consented and asked to permit the surgeons to identify their ureter with the prototype ActivSight™ system during elective laparoscopic surgery after ingesting the proper dosage of riboflavin pre-surgery. Video of the ureter examination will be recorded and analyzed post-surgery; retained video will be devoid of any protected health information.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Center for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ages 22 to 65 presenting for elective laparoscopic abdominopelvic surgery
• No contraindication to riboflavin and able to ingest riboflavin in pill form
• Willing and able to consent to the study
• Native language is English or proficient in both written and spoken English

Exclusion Criteria:

• Known or suspected history of any of the following:

  • Kidney or liver disease
  • Vitamin deficiency or transporter deficiency or metabolic disorder
  • Pelvic surgery (including gynecologic, colorectal, urologic, etc.)
  • Pelvic radiation
  • Abdominopelvic trauma
  • Ureteral injury or presence of ureteral stent(s)
  • Bladder injury
  • Kidney stones
  • Inflammatory bowel disease
  • Neurologic disorder, including seizure or stroke history (history of migraine is acceptable)
  • Any form of diabetes
• Active malignancy
• Uncontrolled hypertension
• Multiple chronic recurring urinary tract infections (isolated urinary tract infections are acceptable)
• BMI > 35 kg/m2
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Investigational Arm; Patients in the investigational arm will ingest 400mg PO riboflavin pre-operatively. At the start of their procedure, after the surgeon gain laparoscopic access using their standard procedures and equipment, the updated version of the ActivSight device will be placed through a standard laparoscopic trocar and attempts will be made to visualize the ureter under direct imaging using light in the visible spectrum. When the surgeon is complete with the attempted visualization, they will remove the ActivSight device and proceed with their normal operative course and equipment. No surgical decisions will be made based upon this information, and the device will only be used during the aforementioned time.

Device: Investigational Safety and Feasibility; Technical feasibility will be assessed based on a five-point rating scale assessing the ease-of-use, ureteral visibility, and time required to identify the ureter using ActivSight™. All images and video of the ureter will be recorded, but surgeon feedback will be used to assess technical success based on a five point scale, rather than these (subsequently de-identified) recordings. Safety will be confirmed through clinical assessments and evaluation of adverse events intraoperatively and through a 28-day follow-up period using the criteria listed below. All adverse events will be adjudicated by the site's Principal Investigator (PI) to judge the relatedness of the adverse event to either the administration of riboflavin or the use of the prototype ActivSight™ device (or whether the adverse event was unrelated to either)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ureteral visibility	1-5 point scale, surgeon assessment of how visible the ureter was on imaging	Immediately post-operative
Ease of use	1-5 point scale, surgeon assessment of how easy the technology was to use intraoperatively	Immediately post-operative
Time required to identify ureter	1-5 point scale, surgeon assessment of how much time it took to identify the ureter	Immediately post-operative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events will be summarized descriptively and tabulations on the type, severity, and relationship to the prototype ActivSight™ or administration of riboflavin will be performed and any changes of outcomes from baseline on follow up will be examined using the nonparametric Wilcoxon rank test.	28 days post-op

Collaborators and Investigators

• Sponsor: Activ Surgical

Publications and helpful links

General Publications

• de Valk KS, Handgraaf HJ, Deken MM, Sibinga Mulder BG, Valentijn AR, Terwisscha van Scheltinga AG, Kuil J, van Esdonk MJ, Vuijk J, Bevers RF, Peeters KC, Holman FA, Frangioni JV, Burggraaf J, Vahrmeijer AL. A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery. Nat Commun. 2019 Jul 16;10(1):3118. doi: 10.1038/s41467-019-11014-1.
• Delacroix SE Jr, Winters JC. Urinary tract injures: recognition and management. Clin Colon Rectal Surg. 2010 Jun;23(2):104-12. doi: 10.1055/s-0030-1254297.
• Andersen P, Andersen LM, Iversen LH. Iatrogenic ureteral injury in colorectal cancer surgery: a nationwide study comparing laparoscopic and open approaches. Surg Endosc. 2015 Jun;29(6):1406-12. doi: 10.1007/s00464-014-3814-1. Epub 2014 Aug 26.
• Engel O, Rink M, Fisch M. Management of iatrogenic ureteral injury and techniques for ureteral reconstruction. Curr Opin Urol. 2015 Jul;25(4):331-5. doi: 10.1097/MOU.0000000000000175.
• Thompson DF, Saluja HS. Prophylaxis of migraine headaches with riboflavin: A systematic review. J Clin Pharm Ther. 2017 Aug;42(4):394-403. doi: 10.1111/jcpt.12548. Epub 2017 May 8.
• Fernando S, Dowling C, Rosamilia A. The role of preoperative oral vitamin B in the cystoscopic assessment of ureteric patency. Int Urogynecol J. 2011 Aug;22(8):947-51. doi: 10.1007/s00192-011-1396-1. Epub 2011 Apr 7.
• Stitely ML, Harlow K, MacKenzie E. Oral Riboflavin to Assess Ureteral Patency During Cystoscopy: A Randomized Clinical Trial. Obstet Gynecol. 2019 Feb;133(2):301-307. doi: 10.1097/AOG.0000000000003063.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2023
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: ureter, advanced imaging, surgery
• Other Study ID Numbers: 600-00012

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: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No