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

NCT06313385 | Active Not Recruiting DMC

• 1 other identifier: 22-10-1180
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Free Flap; Indocyanine Green; Microsurgery; Temperature Change, Body

Outcome Measures

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.

  Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

Secondary Outcomes (6)

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

  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

  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

  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

  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

  Immediate Postoperative, 24 hours after surgery, 72 hours after surgery, 120 hours after surgery

Study Arms (3)

Group 5 mg/mL

EXPERIMENTAL

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

Group 2,5 mg/mL

ACTIVE COMPARATOR

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

Group 0,5 mg/mL

ACTIVE COMPARATOR

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

Indocyanine Green Fluorescence (ICG) DIAGNOSTIC_TEST

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

Group 0,5 mg/mL; Group 2,5 mg/mL; Group 5 mg/mL

Temperature DIAGNOSTIC_TEST

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.

Group 0,5 mg/mL; Group 2,5 mg/mL; Group 5 mg/mL

Transcutaneous oxygen and carbon dioxide pressure DIAGNOSTIC_TEST

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

Group 0,5 mg/mL; Group 2,5 mg/mL; Group 5 mg/mL

Histopathology DIAGNOSTIC_TEST

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

Group 0,5 mg/mL; Group 2,5 mg/mL; Group 5 mg/mL

Hypoxia inducible factor-1 (HIF-1) alpha DIAGNOSTIC_TEST

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.

Group 0,5 mg/mL; Group 2,5 mg/mL; Group 5 mg/mL

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia

Jakarta Pusat, Jakarta Special Capital Region, 10430, Indonesia

Location

MeSH Terms

Conditions

Body Temperature Changes

Interventions

Temperature; Blood Gas Monitoring, Transcutaneous

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thermodynamics; Physical Phenomena; Weather; Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment, Controlled; Environment and Public Health; Oximetry; Blood Gas Analysis; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Investigative Techniques

Study Officials

• Parintosa Atmodiwirjo

  Fakultas Kedokteran Universitas Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants didn't know about indocyanine green (ICG) drug groups as well as the concentration that they received. The ICG was added into the syringe by research assistant without any label near the end of operation time. The ICG injection to the patient was performed by anesthesiologist who didn't know about the concentration at all. Outcome assessor didn't know about the given concentration.
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Center for Advanced Reconstructive Microsurgery, Principal Investigator

Model Details: The population were divided into three equal groups of indocyanine green concentration : 5 milligram per milliliter (mg/mL), 2,5 mg/mL, and 0,5 mg/mL

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: March 15, 2024
• Study Start: January 1, 2023
• Primary Completion: March 29, 2024
• Study Completion: March 29, 2024
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)