Near-infrared Fluorescence Imaging as a Supportive Tool for Localisation of Deep Infiltrating Endometriosis During Laparoscopy

Indocyanine Green and Near-Infrared Vision for Detection of Endometriosis (GRE-Endo Trial)

The aim of the study is to establish a new and more accurate method to visualize the peritoneal changes caused by endometriosis using Indocyanine Green mediated fluorescence imaging. The hypothesis is that Indocyanine Green, a fluorescent dye that has wide applications throughout medicine in identifying vascularity of tissues and neovascularization, could facilitate the localization and excision of endometriotic lesions exploiting the hypervascularization due to the chronic inflammation

Study Overview

• Status: Completed
• Conditions: Pelvic Endometriosis; Endometriosis Outside Pelvis
• Intervention / Treatment: Drug: Indocyanine Green

Detailed Description

Patients were recruited within the clinical routine after indication for laparoscopy under consideration of the inclusion and exclusion criteria.

The first abdominal and pelvi's inspection was made using direct laparoscope visualization under white light conditions. All areas suspected of peritoneal endometriosis were classified as white, black and red lesions and recorded together with their anatomic location in the surgical record for the purposes of subsequent extirpation.

After the first visual inspection the patient was administered with 0.05 - 0.25 mg /(kg BW) Indocyanine Green intravenously. The Indocyanine Green imaging mode of the Olympus Indocyanine Green Imaging System was activated and suspected areas in Indocyanine Green imaging mode were recorded with their corresponding appearance in white light mode.

If suspected areas were visible either in white light or Indocyanine Green imaging mode, specific sample has been taken from these areas.

In addition control biopsy specimens from inconspicuous peritoneum has been taken.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Catholic University Of Sacred Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Suspected endometriosis with necessity for laparoscopic confirmation and resection
• Regular menstrual cycles

Exclusion Criteria:

• Patients younger than 18 years and older than 50 years at time of operation
• Subject with previous history of adverse reaction or allergy to Indocyanine Green, iodine, shellfish or iodine dyes
• Documented allergy to sulfur containing compounds
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Indocyanine Green
• Subject has significant liver disease, cirrhosis or liver insufficiency with abnormal liver function tests (Total bilirubin increased by factor 1.5 than normal and/or serum glutamic oxaloacetic transaminase increased by factor 2 than normal)
• Subject has uremia, serum creatinine (> 2.0 mg/dl)
• Subject has severe coronary heart disease (instable angina pectoris)
• Pregnant or breast-feeding women
• Subject actively participating in another drug, biologic and/or device protocol
• The presence of medical conditions contraindicating general anesthesia or standard surgical approaches
• Subject has any medical condition, which in the judgment of the Investigator and/or designee makes the subject a poor candidate for the investigational procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: Indocyanine Green arm; All the enrolled patients met the inclusion criteria. No patients have been excluded from the study. All patient have been subjected, during laparoscopy, to an accurate inspection of the abdomen and all the visible endometriotic lesions have been described. Subsequently, 0.25 mg /(kg BW) Indocyanine Green were administered intravenously during surgery and a second look of the abdomen and pelvis with the Near Infrared Vision has been made, in order to identify the fluorescent lesions. All the lesions has been described and localized pre and post the Indocyanine Green injection and then removed and properly cataloged

Drug: Indocyanine Green; 0.25 mg /(kg BW) Indocyanine Green PULSION® - PULSION Medical Systems were administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of endometriotic lesions	Optical qualitative assessment through the visual evaluation of a single expert surgeon (presence / absence of fluorescence, due to the injection of the Indocyanine Green and the use of the Near Infrared vision, at the level the of suspected endometriotic lesions)	Intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Localization of occult endometriotic lesion	To detect occult endometriotic lesions, thanks to the fluorescence of the Indocyanine Green, that would remain otherwise not visible to the surgeon eye	Intraoperative
Operatory Time	To assess if the use of Indocyanine Green cause a significant increase of the operatory time	Intraoperative
Complications	To assess if the use of Indocyanine Green increase the percentage of intra and post-operative complications	From operatory room up to 3 days
Side effects	Evaluation of possible side effects related to the use of Indocyanine Green as a fluorescent endometriosis' marker	From operatory room up to 3 days

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Giovanni Scambia, Division of Oncologic Gynecology, Fondazione Policlinico Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2016
• Primary Completion (Actual): February 16, 2017
• Study Completion (Actual): February 16, 2017

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 1, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Indocyanine Green; Deep Infiltrating Endometriosis; Near-Infrared Vision; Occult endometriosis; Invisible endometriosis
• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: GRE-Endo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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