Application of ICG@HSA Complexes in Fluorescence Image-Guided Laparoscopic Anatomical Liver Resection

NCT06219096 | Recruiting

• 1 other identifier: IHLAP2121
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, prospective, randomized controlled trial that aims to compare the efficacy and safety of a new indocyanine green (ICG) administration protocol with the current guideline-recommended protocol for near-infrared (NIR) fluorescence imaging in laparoscopic anatomical hepatic resection. Primary liver cancer is a common malignancy worldwide. Laparoscopic liver resection has become increasingly popular due to its minimally invasive nature. During open and laparoscopic liver resection surgery, ICG, a fluorescent dye, is widely used to visualize liver segments and define tumor margins. However, there is a lack of high-level evidence regarding the timing and dosage of ICG administration in current protocols. In our preliminary study, we discovered a new method of pre-mixing ICG with albumin, which creates a more stable conjugate that could enhance fluorescence imaging during NIR laparoscopic hepatectomy. This study will include 100 patients with primary liver malignancies who are scheduled for laparoscopic anatomical hepatic resection. The patients will be randomly assigned in a 1:1 ratio to either the new ICG-albumin protocol (experimental group) or the standard ICG alone protocol (control group). The primary outcome will be the efficacy of fluorescence imaging, which will be evaluated using a 5-point scoring system by three independent experts. Secondary outcomes will include operation time, blood loss, tumor margin status, complications, length of stay, long-term recurrence, and survival. The hypothesis of this study is that pre-binding ICG with albumin creates a more stabilized fluorescent complex, which could significantly improve the efficacy of fluorescence navigation and hepatectomy outcomes compared to standard ICG alone. This study aims to provide high-quality evidence on optimal protocols for ICG use in laparoscopic fluorescent image-guided liver surgery. The results of this study could help establish standardized guidelines to improve the application of this important navigation technique and enhance surgical precision and outcomes for liver cancer patients worldwide. The study protocol will be approved by the Ethics Review Board and publicly registered before enrollment starts. All participants will be required to provide informed consent. This study will be conducted in compliance with the Declaration of Helsinki and national regulations on human subject protection to ensure ethics, privacy, and safety.

Conditions

Malignant Tumor of Liver; Randomized Controlled Trial

Keywords

Indocyanine green; Laparoscopic anatomical hepatectomy

Outcome Measures

Primary Outcomes (1)

• Fluorescence imaging effect of the live

  The entire surgical video was recorded and then scored by experts

  On the 7th day after surgery

Secondary Outcomes (10)

• Duration of surgery

  At the end of the surgery

• Intraoperative bleeding

  At the end of the surgery

• Conversion to laparotomy

  At the end of the surgery

• Duration of hepatic parenchymal transection

  On the 7th day after surgery

• Number of hemostatic clips used on the liver transection surface

  On the 7th day after surgery

Other Outcomes (2)

• Overall survival

  From date of randomization until death or loss to follow-up, up to 5 years

• Disease-free survival

  From the surgery was completed until disease progression or loss to follow-up, assessed up to 5 years

Study Arms (2)

The new ICG & HSA injection Group (experimental group)

EXPERIMENTAL

After ligation of the targeted hepatic segmental portal vein, a novel ICG protocol is used (0.5mg ICG powder is added to 20mL normal saline containing 500mg human albumin, shaken and allowed to stand for more than 5 minutes to form a stable complex, with final concentrations of ICG 0.025mg/mL and human albumin 25mg/mL). This ICG-albumin conjugate solution is then administered intravenously at a rate of 1mL/min. The infusion is stopped when sufficient fluorescence enhancement is observed in the negative-staining liver regions.

Procedure: NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration

The guideline-recommended ICG injection Group (active comparator group)

ACTIVE COMPARATOR

After ligation of the targeted hepatic segmental portal vein, 2.5mg of ICG (concentration 2.5mg/mL) is administered intravenously as a bolus injection.

Procedure: NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration

Interventions

NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration PROCEDURE

After ligation of the target hepatic segmental portal vein, the novel ICG regimen (0.5 mg ICG powder and 500 mg human serum albumin added to 20 ml saline, shaken and allowed to stand for more than 5 minutes, ICG: 0.025 mg/ml, human serum albumin: 25 mg/ml) was intravenously infused continuously at a rate of 1 ml/min until significant fluorescence imaging appeared in the demarcated area, upon which the infusion was terminated.

The new ICG & HSA injection Group (experimental group)

NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration PROCEDURE

After ligation of the target hepatic segmental portal vein, 2.5 mg of ICG (2.5 mg/ml) was intravenously injected.

The guideline-recommended ICG injection Group (active comparator group)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-75 years old, patients with hepatic malignancies who are undergoing laparoscopic anatomical liver resection;
• Preoperative liver function Child-Pugh grade A or B;
• No contraindications for laparoscopic liver resection;
• Expected survival ≥3 months;
• ECOG PS score 0-1;
• Normal major organ functions, and meet the following laboratory test results within 7 days prior to enrollment: white blood cell (WBC) ≥2.5×10\^9/L, absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet (PLT) ≥75×10\^9/L, hemoglobin (HGB) ≥90g/L; NR ≤1.5xULN; serum creatinine (CT) ≤1.5xULN; total bilirubin (TBI) ≤1.5×upper limit of normal (ULN);
• Patients voluntarily participate and sign informed consent.

You may not qualify if:

• No obvious ischemic demarcation line after intraoperative occlusion or disconnection of target hepatic pedicle, or the liver fluorescence reaches an intensity that interferes with surgery before intraoperative ICG injection.
• Poor hepatic reserve function (ICG R15 ≥ 20%);
• Severe cardiopulmonary diseases, intolerant to general anesthesia and surgery;
• Moderate or large amount of symptomatic ascites or pleural effusion;
• Active bleeding or coagulation abnormalities;
• Hepatic encephalopathy;
• Allergy to ICG;
• History of gastrointestinal bleeding within the past 6 months or definite tendency for gastrointestinal bleeding;
• Severe esophageal gastric varices requiring interventional treatment;
• Objective evidence showing severe impaired pulmonary function such as pulmonary fibrosis;
• Any significant clinical and laboratory abnormalities that the investigator considers affecting safety assessment.

Sponsors & Collaborators

• West China Hospital: lead
• Nanjing Chia-Tai Tianqing Pharmaceutical Company: collaborator

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 614000, China

RECRUITING

Related Publications (11)

• Landsman ML, Kwant G, Mook GA, Zijlstra WG. Light-absorbing properties, stability, and spectral stabilization of indocyanine green. J Appl Physiol. 1976 Apr;40(4):575-83. doi: 10.1152/jappl.1976.40.4.575.

  PMID: 776922 RESULT

• Ishizawa T, Saiura A, Kokudo N. Clinical application of indocyanine green-fluorescence imaging during hepatectomy. Hepatobiliary Surg Nutr. 2016 Aug;5(4):322-8. doi: 10.21037/hbsn.2015.10.01.

  PMID: 27500144 RESULT

• Wang X, Teh CSC, Ishizawa T, Aoki T, Cavallucci D, Lee SY, Panganiban KM, Perini MV, Shah SR, Wang H, Xu Y, Suh KS, Kokudo N. Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery. Ann Surg. 2021 Jul 1;274(1):97-106. doi: 10.1097/SLA.0000000000004718.

  PMID: 33351457 RESULT

• Berardi G, Igarashi K, Li CJ, Ozaki T, Mishima K, Nakajima K, Honda M, Wakabayashi G. Parenchymal Sparing Anatomical Liver Resections With Full Laparoscopic Approach: Description of Technique and Short-term Results. Ann Surg. 2021 Apr 1;273(4):785-791. doi: 10.1097/SLA.0000000000003575.

  PMID: 31460879 RESULT

• Wakabayashi T, Cacciaguerra AB, Abe Y, Bona ED, Nicolini D, Mocchegiani F, Kabeshima Y, Vivarelli M, Wakabayashi G, Kitagawa Y. Indocyanine Green Fluorescence Navigation in Liver Surgery: A Systematic Review on Dose and Timing of Administration. Ann Surg. 2022 Jun 1;275(6):1025-1034. doi: 10.1097/SLA.0000000000005406. Epub 2022 Feb 2.

  PMID: 35121701 RESULT

• Chen H, Wang Y, Xie Z, Zhang L, Ge Y, Yu J, Zhang C, Jia W, Ma J, Liu W. Application Effect of ICG Fluorescence Real-Time Imaging Technology in Laparoscopic Hepatectomy. Front Oncol. 2022 Apr 6;12:819960. doi: 10.3389/fonc.2022.819960. eCollection 2022.

  PMID: 35463377 RESULT

• Itoh S, Tomiyama T, Morinaga A, Kurihara T, Nagao Y, Toshima T, Morita K, Harada N, Mori M, Yoshizumi T. Clinical effects of the use of the indocyanine green fluorescence imaging technique in laparoscopic partial liver resection. Ann Gastroenterol Surg. 2022 Mar 9;6(5):688-694. doi: 10.1002/ags3.12563. eCollection 2022 Sep.

  PMID: 36091307 RESULT

• Liu F, Wang H, Ma W, Li J, Liu Y, Tang S, Li K, Jiang P, Yang Z, He Y, Liu Z, Zhang Z, Yuan Y. Short- and Long-Term Outcomes of Indocyanine Green Fluorescence Navigation- Versus Conventional-Laparoscopic Hepatectomy for Hepatocellular Carcinoma: A Propensity Score-Matched, Retrospective, Cohort Study. Ann Surg Oncol. 2023 Apr;30(4):1991-2002. doi: 10.1245/s10434-022-13027-5. Epub 2023 Jan 16.

  PMID: 36645540 RESULT

• Cai X, Hong H, Pan W, Chen J, Jiang L, Du Q, Li G, Lin S, Chen Y. Does Using Indocyanine Green Fluorescence Imaging for Tumors Help in Determining the Safe Surgical Margin in Real-Time Navigation of Laparoscopic Hepatectomy? A Retrospective Study. Ann Surg Oncol. 2023 Apr;30(4):1981-1987. doi: 10.1245/s10434-022-12893-3. Epub 2022 Dec 9.

  PMID: 36484905 RESULT

• Xu Y, Chen M, Meng X, Lu P, Wang X, Zhang W, Luo Y, Duan W, Lu S, Wang H. Laparoscopic anatomical liver resection guided by real-time indocyanine green fluorescence imaging: experience and lessons learned from the initial series in a single center. Surg Endosc. 2020 Oct;34(10):4683-4691. doi: 10.1007/s00464-020-07691-5. Epub 2020 Jun 4.

  PMID: 32500459 RESULT

• Xie Q, Gao F, Ran X, Zhao X, Yang M, Jiang K, Mao T, Yang J, Li K, Wu H. Application of indocyanine green-human serum albumin complex in fluorescence image-guided laparoscopic anatomical liver resection: study protocol for a randomized controlled trial. Trials. 2024 Dec 23;25(1):847. doi: 10.1186/s13063-024-08695-5.

  PMID: 39710697 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Hong Wu, Professor

  West China Hospital

  STUDY CHAIR

Central Study Contacts

Hong Wu, Professor

CONTACT

18980601958; wuhong@scu.edu.cn

QingYun Xie, MD

CONTACT

18608070908; Dr.Xieqingyun@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study utilizes a double-blind design to ensure impartiality among operators, outcome assessors, and patients. The randomization assignment is only known to the research nurse, who administers the two different ICG administration protocols during surgery based on the assigned randomization number and group allocation. To maintain blinding, an opaque curtain is placed over the anesthesia operation area on the patient's head side, preventing the surgical operator from knowing the randomization assignment. The entire process of grouping and drug delivery is observed solely by the dedicated research nurse. In order to minimize assessment bias, the evaluators and data collectors are also blinded and have no knowledge of the patient's grouping information, thus reducing the potential impact of bias on the results. The efficacy of fluorescence imaging will be evaluated and scored independently by three experts in the field of fluorescence.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 25, 2023
• First Posted: January 23, 2024
• Study Start: December 10, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)