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Randomized Controlled Trial on Effect of Lymph Node Mapping by Indocyanine Green Via Submucosal or Subserosal Injection

Primary Purpose

Indocyanine Green, Gastric Cancer, Injection Site

Status
Active
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Subserosa injection of indocyanine green
submucosal injection of indocyanine green
Sponsored by
Fujian Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Indocyanine Green

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Age from 18 to 75 years
  2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by endoscopic biopsy
  3. Clinical stage tumor T1-4a (cT1-4a), N0/+, M0 at preoperative evaluation according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual Eighth Edition. Preoperative staging was made by conducting mandatory computed tomography (CT) scans and an optional endoscopic ultrasound
  4. No distant metastasis, no direct invasion of pancreas, spleen or other organs nearby in the preoperative examinations
  5. Performance status of 0 or 1 on Eastern Cooperative Oncology Group scale (ECOG)
  6. American Society of Anesthesiology score (ASA) class I, II, or III
  7. Written informed consent

Exclusion criteria:

  1. Women during pregnancy or breast-feeding
  2. Severe mental disorder
  3. History of previous upper abdominal surgery (except laparoscopic cholecystectomy)
  4. History of previous gastrectomy, endoscopic mucosal resection or endoscopic submucosal dissection
  5. Rejection of laparoscopic resection
  6. History of allergy to iodine agents
  7. Enlarged or bulky regional lymph node diameter over 3cm by preoperative imaging
  8. History of other malignant disease within past five years
  9. History of previous neoadjuvant chemotherapy or radiotherapy
  10. History of unstable angina or myocardial infarction within past six months
  11. History of cerebrovascular accident within past six months
  12. History of continuous systematic administration of corticosteroids within one month
  13. Requirement of simultaneous surgery for other disease
  14. Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer
  15. Forced expiratory volume in 1 second (FEV1)<50% of predicted values
  16. Linitis plastica, Widespread

Sites / Locations

  • Department of Gastric Surgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Subserosal injection of indocyanine green tracer group

Submucosal injection of indocyanine green tracer group

Arm Description

Subserosal injection of indocyanine green, with a concentration of 0.5 mg /ml, 6 points along the lesser and greater curvature of the stomach, 1.5 ml for each point.

Submucosal injection of indocyanine green, with a concentration of 1.25mg /ml, four points around the primary tumor, each point 0.5 ml.

Outcomes

Primary Outcome Measures

Total Number of Retrieved Lymph Nodes
Total Number of Retrieved Lymph Nodes

Secondary Outcome Measures

Total number of fluorescent lymph nodes in groups A and B
Total number of fluorescent lymph nodes in groups A and B
Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)
Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)
Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)
Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)
Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)
Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)
Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)
Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)
Number of Metastasis Lymph Nodes
Number of Metastasis Lymph Nodes
Metastasis rate of lymph node
Metastasis rate of lymph node
Mortality rates
This is for the early mortality, which defined as the event observed within 30 days after surgery.
Morbidity rates
This is for the incidence of early postoperative complications, which defined as the event observed within 30 days after surgery.
3-year disease free survival rate
Disease-free survival is calculated from the day of surgery to the day of recurrence or death (When the specific date of recurrence of the tumor is unknown, the endpoint is the date of death due to tumor causes). If neither death nor recurrence of the tumor is observed, the endpoint is the final date that a patient is confirmed as relapse-free. (The final date of DFS: The last date of the outpatient visit day or the date of acceptance of the examination).
3-year recurrence pattern
Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type.
Time to first ambulation
Time to first ambulation in hours is used to assess the postoperative recovery course.
Time to first flatus
Time to first flatus in days is used to assess the postoperative recovery course.
Time to first liquid diet
Time to first liquid diet in days is used to assess the postoperative recovery course.
Time to first soft diet
Time to first soft diet in days is used to assess the postoperative recovery course.
Duration of postoperative hospital stay
Duration of postoperative hospital stay in days is used to assess the postoperative recovery course.
The variation of weight
The variation of weight on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.
The variation of BMI in kg/m^2
The variation of BMI in kg/m^2 on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.
Intraoperative morbidity rates
The intraoperative postoperative morbidity rates are defined as the rates of event observed within operation.
The variation of white blood cell count
The values of white blood cell count from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
The variation of hemoglobin
The values of hemoglobin in gram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
The variation of C-reactive protein
The values of C-reactive protein IN milligram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
Lymph node noncompliance rate
Lymph node noncompliance was defined as the absence of lymph nodes that should have been excised from more than 1 lymph node station. Major lymph node noncompliance was defined as more than 2 intended lymph node stations that were not removed.
Modified EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT14)
Participants were asked to complete one modified European Organisation for Research and Treatment of Cancer (EORTC) IN-PATSAT14 questionnaire before their discharge from hospital.
The Surgery Task Load Index (SURG-TLX)
Surgeons were required to complete one modified SURG-TLX questionnaire for each procedure.
3-year overall survival rate
The overall survival is calculated from the day of surgery until death or until the final follow-up date, whichever occurs first. For survival cases, the endpoint is the last date that survival was confirmed. If the loss to follow-up occurred, the endpoint is the final date that survival could be confirmed.

Full Information

First Posted
January 1, 2020
Last Updated
October 5, 2023
Sponsor
Fujian Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04219332
Brief Title
Randomized Controlled Trial on Effect of Lymph Node Mapping by Indocyanine Green Via Submucosal or Subserosal Injection
Official Title
Comparison of Submucosal and Subserosal Approaches Toward Optimized Indocyanine Green Tracer-Guided Laparoscopic Lymphadenectomy for Patients With Gastric Cancer: The FUGES-019 Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 31, 2019 (Actual)
Primary Completion Date
November 27, 2020 (Actual)
Study Completion Date
October 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fujian Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study was to evaluate whether submucosal or subserous injection of indocyanine green during laparoscopic lymphadenectomy for patients with gastric cancer was different. The patients with gastric adenocarcinoma (cT1-4a, N0/+, M0) were studied.
Detailed Description
In recent years, with the successful application of ICG (indocyanine green) fluorescence imaging technology in laparoscopic equipment, scholars have found that ICG near-infrared imaging has better tissue penetration and can better identify lymph nodes in hypertrophic adipose tissue than other dyes under visible light, which makes ICG fluorescence imaging guide laparoscopic radical resection of gastric cancer lymph node dissection has become a new exploration direction. ICG near-infrared imaging technology has important research value, good application prospects, and broad development space in laparoscopic radical resection of gastric cancer. However, at present, the application of ICG near-infrared imaging technology in laparoscopic radical resection of gastric cancer is still in the exploratory stage, and there is no unified standard. Therefore, in the world, there is still a lack of high-level evidence-based evidence of large-sample prospective randomized controlled trials to evaluate the effectiveness, safety, and feasibility of submucosal or subserous injection of ICG in guiding laparoscopic D2 resection of gastric cancer. The investigator first carried out this study in the world to evaluate the lymph node dissection and perioperative safety of gastric cancer patients who received a submucosal injection of ICG and subserous injection of ICG during laparoscopic radical gastrectomy in the same period, to promote the standardized development of ICG near-infrared imaging in laparoscopic radical gastrectomy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indocyanine Green, Gastric Cancer, Injection Site

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Although it was not feasible to blind the surgeons and participants, the pathologists were unaware of the intervention received by the patients. The researcher performing the statistical analyses was blinded to the patient group allocation.
Allocation
Randomized
Enrollment
266 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Subserosal injection of indocyanine green tracer group
Arm Type
Experimental
Arm Description
Subserosal injection of indocyanine green, with a concentration of 0.5 mg /ml, 6 points along the lesser and greater curvature of the stomach, 1.5 ml for each point.
Arm Title
Submucosal injection of indocyanine green tracer group
Arm Type
Active Comparator
Arm Description
Submucosal injection of indocyanine green, with a concentration of 1.25mg /ml, four points around the primary tumor, each point 0.5 ml.
Intervention Type
Drug
Intervention Name(s)
Subserosa injection of indocyanine green
Other Intervention Name(s)
No other intervention
Intervention Description
After preoperative exploration, the indocyanine green powder (Dandong Yichuang Pharmaceutical Co) is dissolved in 0.5 mg/ml of sterile water and the prepared solution (1.5 ml for each point) is injected along the subserosal of the stomach at 6 specific points along the lesser and greater curvature of the stomach.
Intervention Type
Drug
Intervention Name(s)
submucosal injection of indocyanine green
Other Intervention Name(s)
No other intervention
Intervention Description
One day before surgery, 1.25 mg/ml indocyanine green (Dandong Yichuang Pharmaceutical Co) was prepared in sterile water and 0.5 ml of the solution was injected into the submucosal layer at 4 quadrants around the primary tumor, amounting to 2.5 mg of indocyanine green.
Primary Outcome Measure Information:
Title
Total Number of Retrieved Lymph Nodes
Description
Total Number of Retrieved Lymph Nodes
Time Frame
One month after surgery
Secondary Outcome Measure Information:
Title
Total number of fluorescent lymph nodes in groups A and B
Description
Total number of fluorescent lymph nodes in groups A and B
Time Frame
One month after surgery
Title
Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)
Description
Relationship between fluorescent lymph nodes and positive lymph nodes in groups A and B (true positive rate)
Time Frame
One month after surgery
Title
Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)
Description
Relationship between fluorescent lymph nodes and negative lymph nodes in groups A and B (false positive rate)
Time Frame
One month after surgery
Title
Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)
Description
Relationship between non-fluorescent and negative lymph nodes in groups A and B (true negative rate)
Time Frame
One month after surgery
Title
Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)
Description
Relationship between non-fluorescent lymph nodes and positive lymph nodes in groups A and B (false negative rate)
Time Frame
One month after surgery
Title
Number of Metastasis Lymph Nodes
Description
Number of Metastasis Lymph Nodes
Time Frame
One month after surgery
Title
Metastasis rate of lymph node
Description
Metastasis rate of lymph node
Time Frame
One month after surgery
Title
Mortality rates
Description
This is for the early mortality, which defined as the event observed within 30 days after surgery.
Time Frame
30 days
Title
Morbidity rates
Description
This is for the incidence of early postoperative complications, which defined as the event observed within 30 days after surgery.
Time Frame
30 days
Title
3-year disease free survival rate
Description
Disease-free survival is calculated from the day of surgery to the day of recurrence or death (When the specific date of recurrence of the tumor is unknown, the endpoint is the date of death due to tumor causes). If neither death nor recurrence of the tumor is observed, the endpoint is the final date that a patient is confirmed as relapse-free. (The final date of DFS: The last date of the outpatient visit day or the date of acceptance of the examination).
Time Frame
36 months
Title
3-year recurrence pattern
Description
Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type.
Time Frame
36 months
Title
Time to first ambulation
Description
Time to first ambulation in hours is used to assess the postoperative recovery course.
Time Frame
30 days
Title
Time to first flatus
Description
Time to first flatus in days is used to assess the postoperative recovery course.
Time Frame
30 days
Title
Time to first liquid diet
Description
Time to first liquid diet in days is used to assess the postoperative recovery course.
Time Frame
30 days
Title
Time to first soft diet
Description
Time to first soft diet in days is used to assess the postoperative recovery course.
Time Frame
30 days
Title
Duration of postoperative hospital stay
Description
Duration of postoperative hospital stay in days is used to assess the postoperative recovery course.
Time Frame
30 days
Title
The variation of weight
Description
The variation of weight on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.
Time Frame
3, 6, 9 and 12 months
Title
The variation of BMI in kg/m^2
Description
The variation of BMI in kg/m^2 on postoperative 3, 6, 9 and 12 months are used to access the postoperative nutritional status and quality of life.
Time Frame
3, 6, 9 and 12 months
Title
Intraoperative morbidity rates
Description
The intraoperative postoperative morbidity rates are defined as the rates of event observed within operation.
Time Frame
1 day
Title
The variation of white blood cell count
Description
The values of white blood cell count from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
Time Frame
Preoperative 3 days and postoperative 1, 3, and 5 days
Title
The variation of hemoglobin
Description
The values of hemoglobin in gram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
Time Frame
Preoperative 3 days and postoperative 1, 3, and 5 days
Title
The variation of C-reactive protein
Description
The values of C-reactive protein IN milligram/liter from peripheral blood before operation and on postoperative day 1, 3, 5 are recorded to access the inflammatory and immune response.
Time Frame
Preoperative 3 days and postoperative 1, 3, and 5 days
Title
Lymph node noncompliance rate
Description
Lymph node noncompliance was defined as the absence of lymph nodes that should have been excised from more than 1 lymph node station. Major lymph node noncompliance was defined as more than 2 intended lymph node stations that were not removed.
Time Frame
1 day
Title
Modified EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT14)
Description
Participants were asked to complete one modified European Organisation for Research and Treatment of Cancer (EORTC) IN-PATSAT14 questionnaire before their discharge from hospital.
Time Frame
30 days
Title
The Surgery Task Load Index (SURG-TLX)
Description
Surgeons were required to complete one modified SURG-TLX questionnaire for each procedure.
Time Frame
1 day
Title
3-year overall survival rate
Description
The overall survival is calculated from the day of surgery until death or until the final follow-up date, whichever occurs first. For survival cases, the endpoint is the last date that survival was confirmed. If the loss to follow-up occurred, the endpoint is the final date that survival could be confirmed.
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Age from 18 to 75 years Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by endoscopic biopsy Clinical stage tumor T1-4a (cT1-4a), N0/+, M0 at preoperative evaluation according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual Eighth Edition. Preoperative staging was made by conducting mandatory computed tomography (CT) scans and an optional endoscopic ultrasound No distant metastasis, no direct invasion of pancreas, spleen or other organs nearby in the preoperative examinations Performance status of 0 or 1 on Eastern Cooperative Oncology Group scale (ECOG) American Society of Anesthesiology score (ASA) class I, II, or III Written informed consent Exclusion criteria: Women during pregnancy or breast-feeding Severe mental disorder History of previous upper abdominal surgery (except laparoscopic cholecystectomy) History of previous gastrectomy, endoscopic mucosal resection or endoscopic submucosal dissection Rejection of laparoscopic resection History of allergy to iodine agents Enlarged or bulky regional lymph node diameter over 3cm by preoperative imaging History of other malignant disease within past five years History of previous neoadjuvant chemotherapy or radiotherapy History of unstable angina or myocardial infarction within past six months History of cerebrovascular accident within past six months History of continuous systematic administration of corticosteroids within one month Requirement of simultaneous surgery for other disease Emergency surgery due to complication (bleeding, obstruction or perforation) caused by gastric cancer Forced expiratory volume in 1 second (FEV1)<50% of predicted values Linitis plastica, Widespread
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chang-Ming Huang, MD
Organizational Affiliation
Fujian Medical University Union Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Gastric Surgery
City
Fuzhou
State/Province
Fujian
Country
China

12. IPD Sharing Statement

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15908163
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Randomized Controlled Trial on Effect of Lymph Node Mapping by Indocyanine Green Via Submucosal or Subserosal Injection

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