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Active, not recruitingNCT06313385Updated Mar 15, 2024

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

An interventional study of Indocyanine Green Fluorescence (ICG) and Temperature in Free Flap, Indocyanine Green and Microsurgery, sponsored by Indonesia University. Active, not recruiting at 1 site in Indonesia. Per ClinicalTrials.gov, last updated 2024-03-15.

Sponsored by Indonesia University · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
63
Allocation
Randomized
Sex
All
01

Study summary

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.

Read the 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.
02

Conditions studied

  • Free Flap
  • Indocyanine Green
  • Microsurgery
  • Temperature Change, Body
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
63 participants (estimated)

Study arms

  • 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) · Diagnostic Test: Temperature · Diagnostic Test: Transcutaneous oxygen and carbon dioxide pressure · Diagnostic Test: Histopathology · Diagnostic Test: Hypoxia inducible factor-1 (HIF-1) alpha

  • 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) · Diagnostic Test: Temperature · Diagnostic Test: Transcutaneous oxygen and carbon dioxide pressure · Diagnostic Test: Histopathology · Diagnostic Test: Hypoxia inducible factor-1 (HIF-1) alpha

  • 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) · Diagnostic Test: Temperature · Diagnostic Test: Transcutaneous oxygen and carbon dioxide pressure · Diagnostic Test: Histopathology · Diagnostic Test: Hypoxia inducible factor-1 (HIF-1) alpha

Interventions

  • Diagnostic testIndocyanine 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

    Also known as: ICG fluorescence

  • Diagnostic testTemperature

    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 testTranscutaneous 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 testHistopathology

    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 testHypoxia 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.

05

What researchers measure

Primary outcomes

  1. The Effect of Indocyanine Green Fluorescence Intensity to evaluate free flap perfusion

    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.

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

Secondary outcomes

  1. The ICG fluorescence intensity in different titration dose with flap surface Temperature

    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

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

  2. Correlation between ICG fluorescence intensity in different titration dose with transcutaneous carbon dioxide and oxygen pressure

    The transcutaneous carbon dioxide and oxygen pressure are shown in mmHg after being measured with transcutaneous (TCM) Combi 4 device.

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

  3. Correlation between ICG fluorescence intensity concentration in different titration dose with flap neutrophile count

    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.

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

  4. Correlation between ICG fluorescence intensity concentration in different titration dose with flap necrosis volume

    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.

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

  5. Correlation between ICG fluorescence intensity concentration in different titration dose with vascular flap proliferation of the tissue

    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.

    Time frame: Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

  6. Correlation between ICG fluorescence intensity in different titration dose with HIF-1 Alpha

    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.

    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

06

Study locations

1 site
  • Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia
    Jakarta Pusat, Jakarta 10430, Indonesia
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06313385
Lead sponsor
Indonesia University
Responsible party
Parintosa Atmodiwirjo (Head of Center for Advanced Reconstructive Microsurgery, Principal Investigator, Indonesia University) — Principal investigator
First posted
Mar 15, 2024
Start date
Jan 1, 2023
Primary completion
Mar 29, 2024 (estimated)
Completion
Mar 29, 2024 (estimated)
Last update
Mar 15, 2024

Study contacts

Parintosa Atmodiwirjo
principal investigator · Fakultas Kedokteran Universitas Indonesia

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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