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Prospective Evaluation of Near-infrared Fluorescence Imaging Use as a Supportive Tool in Deep Infiltrating Endometriosis Surgery (GRE-Endo-2)

Primary Purpose

Pelvic Endometriosis, Endometriosis Outside Pelvis

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Indocyanine Green
Sponsored by
Catholic University of the Sacred Heart
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Pelvic Endometriosis focused on measuring indocyanine Green, deep Infiltrating Endometriosis, near-Infrared Vision, occult endometriosis, invisible endometriosis

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Catholic University of Sacred Heart

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Indocyanine Green arm

Arm Description

All the patients to be enrolled have to meet the inclusion criteria. All enrolled patient is subjected, during laparoscopy, to an accurate inspection of the abdomen and all the visible endometriotic lesions are described. Subsequently, 0.25 mg /(kg BW) Indocyanine Green is administered intravenously during surgery and a second look of the abdomen and pelvis with the Near Infrared Vision is made, in order to identify the fluorescent lesions. All the lesions are described and localized pre and post the Indocyanine Green injection and then removed and properly cataloged.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Sensibility and Specificity of Near Infrared Vision with Indocyanine green in 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)
Operatory Time
To assess if the use of Indocyanine Green cause a significant increase of the operatory time
Complications
To assess if the use of Indocyanine Green increase the percentage of intra and post-operative complications
Side effects
Evaluation of possible side effects related to the use of Indocyanine Green as a fluorescent endometriosis' marker

Full Information

First Posted
April 30, 2019
Last Updated
August 3, 2020
Sponsor
Catholic University of the Sacred Heart
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1. Study Identification

Unique Protocol Identification Number
NCT03935165
Brief Title
Prospective Evaluation of Near-infrared Fluorescence Imaging Use as a Supportive Tool in Deep Infiltrating Endometriosis Surgery
Acronym
GRE-Endo-2
Official Title
Indocyanine Green and Near-Infrared Vision in Deep Infiltrating Endometriosis Surgery. A Prospective Study (GRE-Endo-2 Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
January 4, 2016 (Actual)
Primary Completion Date
May 19, 2019 (Actual)
Study Completion Date
May 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Catholic University of the Sacred Heart

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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 neo-vascularization, could facilitate the localization and excision of endometriotic lesions exploiting the hypervascularization due to the chronic inflammation. The already published Pilot Study GRE-ENDO (Cosentino F, Near-Infrared Imaging with Indocyanine Green for Detection of Endometriosis Lesions (Gre-Endo Trial): A Pilot Study.), encouraged the effort of a larger prospective trial. Based on the mini-max two-stage design by Simon [Simon R. Optimal two stage design for phase II clinical trials], the investigators tested the null hypothesis that the true rate of pathologically assessed endometriosis would improve from 87% to the clinically relevant alternative of 100.0%, as assessed by NIR-ICG laparoscopy.
Detailed Description
Patients were recruited within the clinical routine after indication for laparoscopy under consideration of the inclusion and exclusion criteria. The sample size was calculated according to the study design by Simon (Simon R. Optimal two stage design for phase II clinical trials), using an α-error of 0.01 (two-sided) and a β-error of 0.90. Considering a patient dropout of approximately 10%, the study was planned to enrol at least 47 women. The first abdominal and pelvi's inspection was made using direct laparoscope visualization under white light conditions. All areas suspected of peritoneal endometriosis was 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 them 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pelvic Endometriosis, Endometriosis Outside Pelvis
Keywords
indocyanine Green, deep Infiltrating Endometriosis, near-Infrared Vision, occult endometriosis, invisible endometriosis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
In the selected patients, after a first white light visual inspection, 0.25 mg/(kg BW) ICG were injected intravenously. After 15 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)
Allocation
N/A
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Indocyanine Green arm
Arm Type
Experimental
Arm Description
All the patients to be enrolled have to meet the inclusion criteria. All enrolled patient is subjected, during laparoscopy, to an accurate inspection of the abdomen and all the visible endometriotic lesions are described. Subsequently, 0.25 mg /(kg BW) Indocyanine Green is administered intravenously during surgery and a second look of the abdomen and pelvis with the Near Infrared Vision is made, in order to identify the fluorescent lesions. All the lesions are described and localized pre and post the Indocyanine Green injection and then removed and properly cataloged.
Intervention Type
Drug
Intervention Name(s)
Indocyanine Green
Intervention Description
0.25 mg /(kg BW) Indocyanine Green PULSION®/ VERDYE Diagnostic Green® - Indocyanine Green is administered Intravenously
Primary Outcome Measure Information:
Title
Localization of occult endometriotic lesion
Description
To detect occult endometriotic lesions, thanks to the fluorescence of the Indocyanine Green, that would remain otherwise not visible to the surgeon eye
Time Frame
Intraoperative
Secondary Outcome Measure Information:
Title
Sensibility and Specificity of Near Infrared Vision with Indocyanine green in detection of endometriotic lesions
Description
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)
Time Frame
Intraoperative
Title
Operatory Time
Description
To assess if the use of Indocyanine Green cause a significant increase of the operatory time
Time Frame
Intraoperative
Title
Complications
Description
To assess if the use of Indocyanine Green increase the percentage of intra and post-operative complications
Time Frame
From operatory room up to 3 days
Title
Side effects
Description
Evaluation of possible side effects related to the use of Indocyanine Green as a fluorescent endometriosis' marker
Time Frame
From operatory room up to 3 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Cosentino, MD
Organizational Affiliation
Fondazione di Ricerca e Cura Giovanni Paolo II , Campobasso , Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Catholic University of Sacred Heart
City
Rome
State/Province
RM
ZIP/Postal Code
00100
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29551477
Citation
Cosentino F, Vizzielli G, Turco LC, Fagotti A, Cianci S, Vargiu V, Zannoni GF, Ferrandina G, Scambia G. Near-Infrared Imaging with Indocyanine Green for Detection of Endometriosis Lesions (Gre-Endo Trial): A Pilot Study. J Minim Invasive Gynecol. 2018 Nov-Dec;25(7):1249-1254. doi: 10.1016/j.jmig.2018.02.023. Epub 2018 Mar 15.
Results Reference
background
PubMed Identifier
2702835
Citation
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.
Results Reference
result

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Prospective Evaluation of Near-infrared Fluorescence Imaging Use as a Supportive Tool in Deep Infiltrating Endometriosis Surgery

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