Investigating the Impact of Indocyanine Green Titration on Fluorescent Intensity in Free Flap : An Exploration of Alternative Indicators

March 13, 2024 updated by: Parintosa Atmodiwirjo, Indonesia University

The Effect of Indocyanine Green Titration on Fluorescent Intensity Degree in Free Flap : A Lookout to Flap Surface Temperature, TCPO2, TCPCO2, HIF-1 Alpha Expression Level, and Histopathology

This study is a randomized clinical trials that aim to determine the effect of Indocyanine Green (ICG) titration dose on the intensity degree of ICG fluorescence imaging results. In addition, this study will also determine the relationship of other indicators such as flap surface temperature, transcutaneous pressure of carbon dioxide (TcPCO2), transcutaneous pressure of oxygen (TcPCO2), HIF - 1 alpha expression, and flap histopathology morphology to the intensity degree of ICG fluorescence imaging results with titrated doses.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The ICG contrast solution will be evaluated with Near-Infrared (NIR) camera that being fixated 20 cm above the flap after the injection. The imaging result will be analyzed using ImageJ Application to assess the grey value. The fluorescent intensity of ICG will be compared with other tests.

Drop Out Criteria :

  • Patients who are unable to complete the research procedure due to various condition, such as death
  • Patients who experience complications or worsening, during and after surgery.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • Jakarta
      • Jakarta Pusat, Jakarta, Indonesia, 10430
        • Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Free flap operation that being performed by researchers.
  • Free Flap must have a skin paddle located on the body skin area with intraoperative ischemic time of at least 60 Minutes
  • Free flap should be in a viable/vital condition judged from the clinical examination of the flap, which includes color, temperature, turgor, capillary refill time (CRT), and skin prick test, immediately post surgery
  • Body area that will be a flap-free donor area has no history of trauma or operation
  • Patient with blood albumin value >3 gr / dL
  • The patient/family sign the informed consent sheet stating willingness to become research sample

Exclusion Criteria:

  • Patients have increased sensitivity to iodine or ICG
  • Free Flaps that being transported undergo trauma or damage due to external factors during treatment
  • Patient with high urea and creatinine level
  • Patient with high Alanine transaminase (ALT) and Aspartate transaminase (AST) level
  • Patients who receive injectable heparin treatment containing natrium disulfite preoperatively
  • Patients who regularly take anti-seizure drugs, haloperidol, heroin, meperidine, Metamizole, methadone, morphine, nitrofurantoin, opium, phenobarbital, and phenylbutazone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 5 mg/mL
This group received 5 mg/mL concentration of Indocyanine Green (Aurogreen®, Aurolab, Tamil Nadu, India). Indocyanine Green (ICG) is being diluted with 5 mL dextrose 5%. The research assistant take 1 mL ICG using 1 mL syringe using filter that originated from the Aurogreen package.
Diagnostic test: Indocyanine Green Fluorescence (ICG)
The ICG will be injected intravenously and being assessed with Near-infrared (NIR) camera FLUORO4000XL 20 cm above the flap and fluorescence intensity counted with application called ImageJ
Other Names:
  • ICG fluorescence
Diagnostic test: Temperature
Portable thermal imaging camera called Forward-looking infrared (FLIR) ONE® was used to assess flap and normal skin temperature. The FLIR ONE® device was place in perpendicular manner from the skin. The images were attained in two points of times which is direct temperature and after cold challenge test.
Diagnostic test: Transcutaneous oxygen and carbon dioxide pressure
The partial transcutaneous pressure is measured in flap using transcutaneous monitor (TCM) Combi probe. The probe should be cleaned using alcohol pads before use. After 5-10 minutes, the TCM 4 machine monitor should show stable transcutaneous oxygen and carbon dioxide pressure from the flap
Diagnostic test: Histopathology
A part of tissue from free flap is acquired and stored in 10% formalin tube. Later on, the tissue was colored with hematoxylin-eosin, neutrophile count, necrosis volume, and vessel proliferation will be assessed
Diagnostic test: Hypoxia inducible factor-1 (HIF-1) alpha
Peripheral tissue from distal free flap (0,5 x 0,5 cm in size) is obtained and stored in tube with dry ice. The tissue is assessed with human HIF - 1 Alpha Enzyme-Linked Immunosorbent Assay (ELISA) kit ab171577.
Active Comparator: Group 2,5 mg/mL
This group received 2,5 mg/mL concentration of Indocyanine Green (Aurogreen®, Aurolab, Tamil Nadu, India). Indocyanine Green (ICG) is being diluted with 5 mL dextrose 5%. The research assistant take 0,5 mL ICG using 1 mL syringe using filter that originated from the Aurogreen package. The ICG in the syringe is added with 0,5 mL Dextrose 5%.
Diagnostic test: Indocyanine Green Fluorescence (ICG)
The ICG will be injected intravenously and being assessed with Near-infrared (NIR) camera FLUORO4000XL 20 cm above the flap and fluorescence intensity counted with application called ImageJ
Other Names:
  • ICG fluorescence
Diagnostic test: Temperature
Portable thermal imaging camera called Forward-looking infrared (FLIR) ONE® was used to assess flap and normal skin temperature. The FLIR ONE® device was place in perpendicular manner from the skin. The images were attained in two points of times which is direct temperature and after cold challenge test.
Diagnostic test: Transcutaneous oxygen and carbon dioxide pressure
The partial transcutaneous pressure is measured in flap using transcutaneous monitor (TCM) Combi probe. The probe should be cleaned using alcohol pads before use. After 5-10 minutes, the TCM 4 machine monitor should show stable transcutaneous oxygen and carbon dioxide pressure from the flap
Diagnostic test: Histopathology
A part of tissue from free flap is acquired and stored in 10% formalin tube. Later on, the tissue was colored with hematoxylin-eosin, neutrophile count, necrosis volume, and vessel proliferation will be assessed
Diagnostic test: Hypoxia inducible factor-1 (HIF-1) alpha
Peripheral tissue from distal free flap (0,5 x 0,5 cm in size) is obtained and stored in tube with dry ice. The tissue is assessed with human HIF - 1 Alpha Enzyme-Linked Immunosorbent Assay (ELISA) kit ab171577.
Active Comparator: Group 0,5 mg/mL
This group received 2,5 mg/mL concentration of Indocyanine Green (Aurogreen®, Aurolab, Tamil Nadu, India). Indocyanine Green (ICG) is being diluted with 5 mL dextrose 5%. The research assistant take 0,1 mL ICG is taken using 1 mL syringe using filter that originated from the Aurogreen package. The ICG in the syringe is added with 0,9 mL Dextrose 5%.
Diagnostic test: Indocyanine Green Fluorescence (ICG)
The ICG will be injected intravenously and being assessed with Near-infrared (NIR) camera FLUORO4000XL 20 cm above the flap and fluorescence intensity counted with application called ImageJ
Other Names:
  • ICG fluorescence
Diagnostic test: Temperature
Portable thermal imaging camera called Forward-looking infrared (FLIR) ONE® was used to assess flap and normal skin temperature. The FLIR ONE® device was place in perpendicular manner from the skin. The images were attained in two points of times which is direct temperature and after cold challenge test.
Diagnostic test: Transcutaneous oxygen and carbon dioxide pressure
The partial transcutaneous pressure is measured in flap using transcutaneous monitor (TCM) Combi probe. The probe should be cleaned using alcohol pads before use. After 5-10 minutes, the TCM 4 machine monitor should show stable transcutaneous oxygen and carbon dioxide pressure from the flap
Diagnostic test: Histopathology
A part of tissue from free flap is acquired and stored in 10% formalin tube. Later on, the tissue was colored with hematoxylin-eosin, neutrophile count, necrosis volume, and vessel proliferation will be assessed
Diagnostic test: Hypoxia inducible factor-1 (HIF-1) alpha
Peripheral tissue from distal free flap (0,5 x 0,5 cm in size) is obtained and stored in tube with dry ice. The tissue is assessed with human HIF - 1 Alpha Enzyme-Linked Immunosorbent Assay (ELISA) kit ab171577.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The Effect of Indocyanine Green Fluorescence Intensity to evaluate free flap perfusion
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The fluorescence of ICG that being captured with near-infrared (NIR) camera is store in video file to be evaluated. The video duration is 2 minutes long after ICG injection. The fluorescence intensity of the flap in the video is being measured with ImageJ application. The highest level of intensity (numerical data) is considered as the optimal fluorescence intensity that being analyzed later on. The optimal indocyanine green titration will be seen after ImageJ analysis in numerical data called gray values.
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The ICG fluorescence intensity in different titration dose with flap surface Temperature
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The surface temperature of the flap and the surrounding normal tissue is being measured with mobile thermal camera. The temperature result is shown in celsius degree
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
Correlation between ICG fluorescence intensity in different titration dose with transcutaneous carbon dioxide and oxygen pressure
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The transcutaneous carbon dioxide and oxygen pressure are shown in mmHg after being measured with transcutaneous (TCM) Combi 4 device.
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
Correlation between ICG fluorescence intensity concentration in different titration dose with flap neutrophile count
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The neutrophile count is shown as cells per high power field. The high power field in this study is 20x optical view magnification in microscope. This is part of histopathology examination.
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
Correlation between ICG fluorescence intensity concentration in different titration dose with flap necrosis volume
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The necrosis volume result is shown in numerical data percentage (%). High power field which is 20x optical view magnification in microscope. This is part of histopathology examination.
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
Correlation between ICG fluorescence intensity concentration in different titration dose with vascular flap proliferation of the tissue
Time Frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The vascular flap proliferation can be seen using after the tissue sample is stained immunohistochemically using cluster of differentiation (CD) 31 marker in 20x optical view magnification using microscope. The result will be seen in numerical data. This is part of histopathology examination.
Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
Correlation between ICG fluorescence intensity in different titration dose with HIF-1 Alpha
Time Frame: Intraoperative (before start of anastomosis and before end of anastomosis time), 24 hours after surgery, 72 hours after surgery, 120 hours after surgery
The ICG fluorescence intensity in 3 different titration dose will be compared with HIF-1 Alpha. The HIF-1 Alpha will be shown as numerical value in ng/mg of proteins.
Intraoperative (before start of anastomosis and before end of anastomosis time), 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indonesia University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Parintosa Atmodiwirjo, Fakultas Kedokteran Universitas Indonesia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 29, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 29, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 15, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 22-10-1180

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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