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Malignant Tumor of LiverNCT06219096

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

A study testing NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration and NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration in people with Malignant Tumor of Liver and Randomized Controlled Trial, run by West China Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration and NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteChina
Study dates
10 Dec 2023to 31 Dec 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Hong Wu, Professor contact

18980601958

wuhong@scu.edu.cn

QingYun Xie, MD contact

18608070908

Dr.Xieqingyun@gmail.com

China1 site, 1 recruiting

  • West China Hospital

    Chengdu, Sichuan, 614000

    Hong Wu, Professor, +86 18980601958, wuhong@scu.edu.cn

    Qingyun Xie, MD

    Recruiting

Other trials in China

About this study

Official title: Application of Indocyanine Green(ICG)@Human Serum Albumin(HSA) Complexes in Fluorescence Image-Guided Laparoscopic Anatomical Liver Resection: A Prospective, Double-Blinded, Randomized Controlled Trial

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.

Read the detailed description
  1. Study Design: This study is designed as a single center, prospective, randomized, double-blinded, controlled trial. The participants will be randomly assigned to either the experimental group (using the new ICG-albumin protocol) or the control group (using the standard ICG protocol) at a 1:1 ratio. The randomization will be done using a centralized web-based system.
  2. Participants: The study aims to enroll 100 patients aged 18-75 years old with primary liver malignancies who are planned for laparoscopic anatomical hepatic resection at our institution. The main inclusion criteria are a Child-Pugh grade A or B liver function and an ECOG performance score of 0-1. The main exclusion criteria include an ICG R15 value of >=20%, coagulation disorders, severe heart/lung disease, active bleeding, allergy to ICG, severe gastroesophageal varices, and pregnancy/lactation.
  3. Interventions: The interventions in the experimental group will involve mixing 0.5mg of ICG powder with 20mL saline containing 500mg of human albumin for at least 5 minutes. This mixture will then be intravenously infused at a rate of 1mL/min after occlusion of the target hepatic pedicles. On the other hand, the control group will receive a slow intravenous infusion of 2.5mg ICG (2.5mg/mL) following the current guidelines after pedicle occlusion.
  4. Outcomes: The primary outcome is the efficacy of fluorescence imaging, which will be evaluated by a 5-point scoring system by three independent experts. Secondary outcomes include operation time, blood loss, conversion to open surgery, parenchymal transection time, use of hemostatic clips, tumor margins, postoperative complications, liver function recovery, length of stay, long-term recurrence and survival. Safety outcomes include complications, mortality, and adverse reactions associated with ICG.
  5. Participant Timeline: Screening will take place within 2 weeks before surgery. Participants will be followed up during hospitalization. After discharge, follow-up will take place at month 1, 3, 6, 12, 18, 24, 30, 36 post-surgery.
  6. Sample Size: With a two-sided 0.05 significance level, 90% power, and expecting a 1-point improvement in fluorescence imaging efficacy score (SD 1.5), 49 participants per group are needed, 100 in total.
  7. Data Collection and Management: All data will be collected on paper case report forms and then entered into a centralized electronic data capture system. Data will go through quality check, cleaning, coding and logic validation. Any changes will be tracked. Cleaned and locked database will be used for final analysis. Original forms will be archived securely.
  8. Statistical Analysis : Efficacy of fluorescence imaging will be compared between groups using t-test or Mann-Whitney U test. Operation parameters will be analyzed by t-test or Wilcoxon rank test. Tumor margins will be evaluated by chi-square test. Complication rates will be compared using t-test or Fisher's exact test. Survival outcomes will be depicted by Kaplan-Meier curves and compared by Log-rank tests. Multivariate Cox regression will be used to identify factors affecting recurrence and survival. Sensitivity analysis will be performed to account for missing data.
  9. Data Monitoring: An independent data safety monitoring board will review study progress and safety data regularly. Any serious adverse events will be reported to investigators, IRB and regulatory agencies within 24 hours.
  10. Ethics and Dissemination and Trial Status:

The study protocol will be approved by the IRB before initiation. All participants will provide written informed consent. Results will be disseminated through scientific conferences and peer-reviewed publications. The study is currently preparing for ethics submission and enrollment is expected to start in December 2023 and complete in November 2026.

Being tested
NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration, NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration
Keywords
Indocyanine green, Laparoscopic anatomical hepatectomy
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administrationProcedure or surgery

    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.

  • NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administrationProcedure or surgery

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

Study groups in NCT06219096
Study groupRoleWhat they receive
The new ICG & HSA injection Group (experimental group)ExperimentalAfter 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.
Receives: Procedure: NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration
The guideline-recommended ICG injection Group (active comparator group)Active comparatorAfter ligation of the targeted hepatic segmental portal vein, 2.5mg of ICG (concentration 2.5mg/mL) is administered intravenously as a bolus injection.
Receives: Procedure: NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fluorescence imaging effect of the live

    The entire surgical video was recorded and then scored by experts

    Measured: On the 7th day after surgery

Secondary outcomes (10)

  1. Duration of surgery

    Based on the duration of the surgery as recorded

    Measured: At the end of the surgery

  2. Intraoperative bleeding

    Based on the amount of bleeding recorded during the surgery

    Measured: At the end of the surgery

  3. Conversion to laparotomy

    Based on intraoperative records to determine whether to convert to open laparotomy

    Measured: At the end of the surgery

  4. Duration of hepatic parenchymal transection

    Organize a dedicated person to review the surgical video and record the duration after the surgery is over

    Measured: On the 7th day after surgery

  5. Number of hemostatic clips used on the liver transection surface

    Organize a dedicated person to review the surgical video and record the duration after the surgery is over

    Measured: On the 7th day after surgery

  6. Tumor margins

    Specimen tumor margins will be measured by pathologists using calipers

    Measured: At the end of the surgery

  7. Postoperative complications

    Organize a dedicated person to record postoperative complications

    Measured: Up to 24 weeks after surgery

  8. Postoperative hepatic function

    Regularly measure liver function, coagulation, and other biochemical indicators after surgery after the patient returned to the ward

    Measured: Up to 4 weeks after surgery

  9. Postoperative bowel function recovery time

    Organize a dedicated person to record the time of rectal gas passage after surgery afer he patient returned to the ward

    Measured: Up to 2 weeks after surgery

  10. Postoperative hospital stay

    Organize a dedicated person to record the postoperative hospital stay

    Measured: On the second day after discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2024
  2. Study start10 Dec 2023
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06219096
Sponsor's protocol ID
IHLAP2121
Status last verified
Jan 2024
First submitted
25 Dec 2023
Last updated
23 Jan 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 776922

  • 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.

    PubMed 27500144

  • 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.

    PubMed 33351457

  • 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.

    PubMed 31460879

  • 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.

    PubMed 35121701

  • 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.

    PubMed 35463377

  • 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.

    PubMed 36091307

  • 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.

    PubMed 36645540

  • 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.

    PubMed 36484905

  • 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.

    PubMed 32500459

  • 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.

    PubMed 39710697

Questions about this trial

What is this clinical trial studying?

A study testing NIF image-guided laparoscopic anatomical liver resection with the novel ICG@HSA administration and NIF image-guided laparoscopic anatomical liver resection with the guideline-recommended ICG administration in people with Malignant Tumor of Liver and Randomized Controlled Trial, run by West China Hospital at 1 site in China.

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 7 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: looking for participants now, as of the sponsor's last update on 23 Jan 2024. 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 China. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Hong Wu, Professor (18980601958, wuhong@scu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fluorescence imaging effect of the live (time frame: On the 7th day after surgery). 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 NCT06219096, which also lists 11 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 23 Jan 2024.

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