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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Pelvic Endometriosis, Endometriosis Outside Pelvis

Intervention / Treatment
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* Drug: Indocyanine Green


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: In the selected patients, after a first white light visual inspection, 0.25 mg/(kg BW) ICG were injected intravenously. After 5 to 30 minutes a second inspection of the abdomen and pelvis in Near Infrared vision was made. All the visualized lesions were carefully described pre and post the Indocyanine Green injection, removed and listed
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indocyanine Green arm<br>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<br>* 0.25 mg /(kg BW) Indocyanine Green PULSION® - PULSION Medical Systems were administered intravenously<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Indocyanine Green, Deep Infiltrating Endometriosis, Near-Infrared Vision, Occult endometriosis, Invisible endometriosis