Autofluorescence and Indocyanine Green to Avoid Hypocalcemia After Thyroidectomy

April 4, 2024 updated by: Klaas Van Den Heede, Onze Lieve Vrouw Hospital

The Use of Autofluorescence and Indocyanine Green to Avoid Hypocalcemia After Total Thyroidectomy: A Randomized Clinical Trial

  • Hypoparathyroidism (and the resulting hypocalcemia) remains the most common morbidity after a total thyroidectomy.
  • The identification and preservation of parathyroid glands during neck surgery has always been challenging but is crucial to avoid postoperative hypocalcemia.
  • Recently, the specific autofluorescent characteristics of endogenous fluorophores in the parathyroid tissue have been used to detect and confirm parathyroid glands during thyroid surgery.
  • Injecting indocyanine green and using its fluorescent characteristics has the advantage of adding information about the vascular supply of the parathyroid glands.
  • This randomized clinical trial aims to investigate whether using autofluorescence and indocyanine green during thyroid surgery can predict or prevent postoperative hypocalcemia.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Hypoparathyroidism (and the resulting hypocalcemia) remains the most common morbidity after a total thyroidectomy. When defined as corrected serum calcium levels below 2.10 mmol/L, the temporary rates of hypocalcemia after a total thyroidectomy excluding lymph node neck dissection still easily exceed 20% (BAETS fifth national audit report, 2017). When extending the follow-up period to more than six months after surgery, late or permanent hypocalcemia is seen in over 5% of patients after a total thyroidectomy. These British numbers have been confirmed in large European and American databases. A large, Belgian, single-center analysis, including redo-surgery and lymph node neck dissections, confirmed temporary and permanent rates of hypocalcemia of 32% and 3%, respectively.

While temporary hypocalcemia results in a reduced quality of life, additional medical costs to the patients and the society, and hypocalcemia-related symptoms, permanent hypocalcemia adds an increased risk of developing renal failure, basal ganglia calcifications, neuropsychiatric derangements, and infections.

The identification and preservation of parathyroid glands during neck surgery has always been challenging but is crucial to avoid postoperative hypocalcemia. The visual evaluation of parathyroid gland vascularization is even more challenging, prone to subjectivity, and depending on surgical experience and surgical volume. Moreover, even experienced endocrine surgeons appear to be unreliable in using visual scores to assess the viability of parathyroid glands.

Recently, the specific autofluorescent characteristics of endogenous fluorophores in the parathyroid tissue have been used to detect and confirm parathyroid glands during thyroid surgery. However, this signal does not provide any information on viability and vascularization of the parathyroid glands. Injecting indocyanine green (ICG) and using its fluorescent characteristics has the advantage of adding information about the vascular supply of the parathyroid glands. The combined technique of autofluorescent and ICG-enhanced imaging suffers from lack of standardization, optimal technique, dosage, and timing of the ICG administration, and still must prove its possible benefit in a clinical setting.

Hence, this randomized clinical trial aims to investigate whether using autofluorescence (AF) and indocyanine green during thyroid surgery can predict or prevent postoperative hypocalcemia. By using parathyroid gland detection via autofluorescence imaging and verifying their viability after ICG injection, the authors aim to identify patients at risk of hypocalcemia.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All adult patients undergoing a total thyroidectomy without previous neck surgery.

Exclusion Criteria:

  • Children and teenagers (<18 years old)
  • Patients refusing participation or unable/unwilling to sign the informed consent
  • Patients with a completion thyroidectomy
  • Patients with planned central and lateral neck lymph node dissections (thyroid cancer)
  • Patients with previous neck surgery
  • Patients with a known allergy/hypersensitivity to indocyanine green

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autofluorescent detection and injection of indocyanine green

Drug: indocyanine green (ICG)

Autofluorescence detection of the parathyroid glands and injection of indocyanine green at two predefined timepoints will be performed to evaluate the vascularization of the parathyroid glands.
Drug: Autofluorescent detection + Injection of indocyanine green

All four parathyroid glands will be actively sought for in every case selected for the use of AF/ICG, with AF verification of parathyroid tissue.

The timepoints of AF will be:

  • 1 = after lateral dissection side 1 (side 1)
  • 2= after lateral dissection side 2 (side 2)

The timepoints of ICG injection will be:

  • 1 = after the first thyroid lobectomy (side 1)
  • 2 = after the second thyroid lobectomy (side 2)

Scoring of the viability of parathyroid glands (adapted from Vidal Fortuny et al., 2016):

  • 1 = black = not viable/vascularized
  • 2 = grey = moderately viably/ moderately vascularized
  • 3 = white = viable/well-vascularized
Other Names:
  • ICG Injection
Placebo Comparator: Control group
Gold standard of visual identification and evaluation of viability.
Procedure: Gold standard of visual identification and evaluation of viability of the parathyroid glands.
Gold standard of visual identification and evaluation of viability of the parathyroid glands.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative hypocalcemia
Time Frame: One week after surgery
Defined as parathyroid hormone (PTH) levels <15 pg/mL, serum calcium levels <2.10 mmol/L, or the intake of calcium or activated vitamin D supplements after total thyroidectomy.
One week after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of identified parathyroid glands
Time Frame: 1 hour after surgery
Visual identification and confirmation with autofluorescence
1 hour after surgery
The number of reimplanted parathyroid glands
Time Frame: 1 hour after surgery
Visual identification and decision to re-implant after ICG
1 hour after surgery
The presence of late or permanent hypocalcemia
Time Frame: Six months after surgery
Defined as persistent PTH levels <15 pg/mL, persistent serum calcium levels <2.10 mmol/L, or continued intake of calcium or activated vitamin D supplements more than six months after surgery.
Six months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onze Lieve Vrouw Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2021

Primary Completion (Estimated)

October 31, 2024

Study Completion (Estimated)

May 31, 2025

Study Registration Dates

First Submitted

October 21, 2021

First Submitted That Met QC Criteria

November 2, 2021

First Posted (Actual)

November 11, 2021

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B1262021000021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All collected data that underlie results in a publication.

IPD Sharing Time Frame

Data will be available from 1 year after till 20 years after final study completion.

IPD Sharing Access Criteria

Data access request will be reviewed by the ethics committee of the Onze Lieve Vrouw Hospital, Aalst. Any request will require signing and completing a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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