Near-infrared Fluorescence With Indocyanine Green for Identification of Sentinels and Parathyroids During Thyroidectomy

Near-infrared (NIR) Fluorescence Imaging With Indocyanine Green (ICG) for Identification of Sentinel Lymph Nodes and Parathyroid Glands During Total Thyroidectomy: Prospective Randomized Clinical Trial

Indocyanine green (ICG) is a water-soluble organic dye that is cleared totally through the hepatobiliary system. It has a half-life of 3-4 mins, which allows repeated applications. Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) imaging has been recently introduced, and has been suggested as a useful tool for the identification and preservation of the parathyroid glands (PGs) during total thyroidectomy (TT). ICG can also be used for sentinel lymph node (SLN) biopsy to predict the micrometastases in central lymph nodes (CLN) in thyroid carcinoma, and central lymph node dissection can reduce local recurrence.

Study Overview

• Status: Unknown
• Conditions: Thyroid Neoplasms; Sentinel Lymph Node; Thyroid Cancer; Lymph Node Metastases; Thyroid Carcinoma, Papillary; Thyroid Metastases
• Intervention / Treatment: Procedure: Total thyroidectomy (TT); Procedure: Central lymph node dissection (CLND); Diagnostic test: Sentinel lymph node (SLN) bopsy; Diagnostic test: Identification of parathyroid glands (PGs)

Detailed Description

Incidence of thyroid cancer has doubled between 1980 and 2020, and it is now the fifth most common malignant tumor among women. The majority are papillary thyroid cancer (PTC), and TT is the procedure of choice. Since the micrometastasis rate of the central lymph nodes (CLNs) is about 30% to 90% in PTC, CLN dissection can improve the prognosis and reduce tumor recurrence as well as provide accurate information for the evaluation of tumor staging. However, TT procedure has some important complications such as vocal cord paralysis (VCP) and hypocalcemia (due to accicental parathyroidectomy or damage to the parathyroid gland-PG- vasculature). Use of intraoperative nerve monitoring (IONM) has reduced the rate of VCP. However, the incidence of postoperative hypocalcemia is still high (15-70%), and it is now the most common complication of TT. Intraoperative identification of SLNs and PGs can help surgeon to overcome these problems.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34760
    • Recruiting
    • Umraniye Education and Research Hospital, Department of General Surgery
    • Contact: Sema Yuksekdag, MD; Phone Number: 1950 +90 216 632 1818; Email: drsemayuksekdag@gmail.com
    • Contact: Ethem Unal, MD, PhD, A. Prof. of Surgery & Surgical Oncology; Phone Number: 1950 +90 216 632 1818; Email: drethemunal@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 76 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Thyroid carcinoma patients (biopsy/cytology-proven) suitable for total thyroidectomy procedure
• Patients at or over 17 years

Exclusion Criteria:

• Previous thyroid surgery
• Patients below 17 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thyroid carcinoma patients (biopsy-proven)-Total thyroidectomy; Control group-Total thyroidectomy (TT) with central lymph node dissection (CLND) procedure for patients with papillary thyroid carcinoma (PTC) Standard TT+CLND procedure only	Procedure: Total thyroidectomy (TT); Standard TT procedure for thyroid carcinoma, for both groups; Procedure: Central lymph node dissection (CLND); Standard CLND for thyroid carcinoma, for both groups
Experimental: Thyroid carcinoma patients (biopsy-proven)-Sentinel lymph node; Experimental group- Sentinel lymph node dissection (SLND) after intratumoral indocyanine green (ICG) injection and visualization of all 4 parathyroid glands with infra-red (NIR) fluorescence after intravenous (iv) ICG injection, during total thyroidectomy and central lymph node dissection (CLND). TT+CLND with NIR fluorescence ICG	Procedure: Total thyroidectomy (TT); Standard TT procedure for thyroid carcinoma, for both groups; Procedure: Central lymph node dissection (CLND); Standard CLND for thyroid carcinoma, for both groups; Diagnostic test: Sentinel lymph node (SLN) bopsy; Intrathyroidal injection of ICG for SL biopsy, for only experimental group; Diagnostic test: Identification of parathyroid glands (PGs); Near-infrared (NIR) fluorescence visualization of PGs, for only experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Involvement of sentinel lymph node (presence/absence of tumor cell: positive or negative) by histopathological examinatiion	Intrathyroidal injection of indocyanine green (ICG) dye to identify sentinel lymph node (SLN) for biopsy	1 year
Identification of parathyroid glands (PGs) by NIR/ICG camera detected high-contrast	İntravenous injection of ICG dye, to identify PGs under NIR (High-contrast fluorescence seen or not)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central lymph node dissetion (CLND)	Number of positive lymph nodes (micrometastases)	1 year

Collaborators and Investigators

• Sponsor: Umraniye Education and Research Hospital

Publications and helpful links

General Publications

• Zhang X, Shen YP, Li JG, Chen G. Clinical feasibility of imaging with indocyanine green combined with carbon nanoparticles for sentinel lymph node identification in papillary thyroid microcarcinoma. Medicine (Baltimore). 2019 Sep;98(36):e16935. doi: 10.1097/MD.0000000000016935.
• Spartalis E, Ntokos G, Georgiou K, Zografos G, Tsourouflis G, Dimitroulis D, Nikiteas NI. Intraoperative Indocyanine Green (ICG) Angiography for the Identification of the Parathyroid Glands: Current Evidence and Future Perspectives. In Vivo. 2020 Jan-Feb;34(1):23-32. doi: 10.21873/invivo.11741.

Helpful Links

• Ethem Unal

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: June 2, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 5, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Indocyanine green (ICG); Total thyroidectomy; Parathyroid glands; Near-infrared (NIR) fluorescence; Central lymph node dissection
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplastic Processes; Neoplasms, Squamous Cell; Adenocarcinoma, Papillary; Neoplasm Metastasis; Thyroid Diseases; Lymphatic Metastasis; Thyroid Neoplasms; Thyroid Cancer, Papillary; Carcinoma, Papillary; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Parathyroid Hormone
• Other Study ID Numbers: B.10.1.TKH.4.34.H.GP.0.01/213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Excel data is available upon request at drethemunal@gmail.com
• IPD Sharing Time Frame: 1 year
• IPD Sharing Access Criteria: Please request study protocol and data (when available) at drethemunal@gmail.com
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No