Pelvic EndometriosisPhase 2GRE-Endo-2NCT03935165
Prospective Evaluation of Near-infrared Fluorescence Imaging Use as a Supportive Tool in Deep Infiltrating Endometriosis Surgery
A Phase 2 study testing Indocyanine Green in people with Pelvic Endometriosis and Endometriosis Outside Pelvis, run by Catholic University of the Sacred Heart at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Pelvic Endometriosis, Endometriosis Outside Pelvis
- What is being tested?
- Indocyanine Green
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteItaly
- Study dates
- 4 Jan 2016to 19 May 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Suspected endometriosis with necessity for laparoscopic confirmation and resection
- Regular menstrual cycles
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Indocyanine Green and Near-Infrared Vision in Deep Infiltrating Endometriosis Surgery. A Prospective Study (GRE-Endo-2 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 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.
Read the 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.
- Conditions
- Pelvic Endometriosis, Endometriosis Outside Pelvis
- Being tested
- Indocyanine Green
- Keywords
- indocyanine Green, deep Infiltrating Endometriosis, near-Infrared Vision, occult endometriosis, invisible endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indocyanine GreenDrug
0.25 mg /(kg BW) Indocyanine Green PULSION®/ VERDYE Diagnostic Green®
- Indocyanine Green is administered Intravenously
| Study group | Role | What they receive |
|---|---|---|
| Indocyanine Green arm | Experimental | 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. Receives: Drug: Indocyanine Green |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Intraoperative
Secondary outcomes (4)
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)
Measured: Intraoperative
Operatory Time
To assess if the use of Indocyanine Green cause a significant increase of the operatory time
Measured: Intraoperative
Complications
To assess if the use of Indocyanine Green increase the percentage of intra and post-operative complications
Measured: 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
Measured: From operatory room up to 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2019
- Study start4 Jan 2016
- Primary completion19 May 2019
- Study completion19 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pelvic EndometriosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catholic University of the Sacred Heart
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Giovanni Scambia, Catholic University of the Sacred Heart
- Investigators
- Francesco Cosentino, MD, Principal investigator, Fondazione di Ricerca e Cura Giovanni Paolo II , Campobasso , Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03935165
- Sponsor's protocol ID
- 736513. A 287 / C.E./2013
- Acronym
- GRE-Endo-2
- Status last verified
- Aug 2020
- First submitted
- 30 Apr 2019
- Last updated
- 5 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29551477Simon 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.
PubMed 2702835
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Indocyanine Green and Near-Infrared Vision in Deep Infiltrating Endometriosis Surgery. A Prospective Study (GRE-Endo-2 Trial)
- ClinicalTrials.gov ID
- NCT03935165
- Acronym / sponsor ID
- GRE-Endo-2 / 736513. A 287 / C.E./2013
- Conditions
- Pelvic Endometriosis, Endometriosis Outside Pelvis
- Keywords
- indocyanine Green, deep Infiltrating Endometriosis, near-Infrared Vision, occult endometriosis, invisible endometriosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Catholic University of the Sacred HeartUniversity, hospital or other
- Study start
- 4 Jan 2016 (actual)
- Primary completion
- 19 May 2019 (actual)
- Study completion
- 19 May 2019 (actual)
- First posted
- 2 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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
| Arm | Type | Receives |
|---|---|---|
| Indocyanine Green arm | Experimental | Drug: Indocyanine GreenAll 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Suspected endometriosis with necessity for laparoscopic confirmation and resection
- Regular menstrual cycles
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Indocyanine Green0.25 mg /(kg BW) Indocyanine Green PULSION®/ VERDYE Diagnostic Green® - Indocyanine Green is administered Intravenously | Drug | Indocyanine Green arm |
Primary outcome
Localization of occult endometriotic lesion
Time frame: Intraoperative
To detect occult endometriotic lesions, thanks to the fluorescence of the Indocyanine Green, that would remain otherwise not visible to the surgeon eye
4 secondary outcomes
Sensibility and Specificity of Near Infrared Vision with Indocyanine green in detection of endometriotic lesions
Time frame: Intraoperative
Operatory Time
Time frame: Intraoperative
Complications
Time frame: From operatory room up to 3 days
Side effects
Time frame: From operatory room up to 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Background: PubMed 29551477Cosentino 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 publication: PubMed 2702835Simon 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Cosentino, MD principal investigator
Fondazione di Ricerca e Cura Giovanni Paolo II , Campobasso , Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Indocyanine Green in people with Pelvic Endometriosis and Endometriosis Outside Pelvis, run by Catholic University of the Sacred Heart at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Localization of occult endometriotic lesion (time frame: Intraoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03935165, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2020.