Evaluation of Indocyanine Green Angiography for Parathyroid Detection and Hypoparathyroidism Prevention Post-Thyroidectomy in Patients with Thyroid Disorders

The primary objective of this study is to compare the incidence of **albumin-corrected hypocalcaemia** (blood calcium less than 2 mmol/L, a sign associated with hypoparathyroidism) postoperatively between the group using **indocyanine green** and the group not using indocyanine green. This is clinically relevant as hypocalcaemia is a common complication following total thyroidectomy, and its prevention is crucial for patient safety and recovery.

Secondary objectives include:

• Assessing the contribution of indocyanine green angiography in modifying the rate of definitive hypoparathyroidism after total thyroidectomy at various time points (D8, M1, M6).
• Determining the role of indocyanine green angiography during total thyroidectomy for in vivo location and preservation of the parathyroids.
• Evaluating the contribution of indocyanine green angiography in predicting postoperative hypocalcaemia.
• Determining the value of indocyanine green angiography in predicting hypoparathyroidism after total thyroidectomy.
• Comparing the frequency of postoperative hypocalcaemia, according to its grade (mild, moderate, and profound), between the group using indocyanine green and the group not using it.
• Assessing the tolerance of indocyanine green.

The clinical trial involves participants diagnosed with **thyroid diseases**, **hypoparathyroidism**, and **hypocalcemia**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The trial does not focus on a vulnerable population. Participants were selected based on their requirement for a total thyroidectomy, their ability to provide signed consent, and coverage by a social security scheme. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **indocyanine green** angiography in detecting parathyroids and preventing hypoparathyroidism following total thyroidectomy. This is a phase 3, randomized, double-blind, controlled study. The trial aims to compare the incidence of albumin-corrected hypocalcemia, a condition associated with hypoparathyroidism, between two groups: one using indocyanine green and the other not using it. The primary endpoint is the occurrence of albumin-corrected hypocalcemia (≤2 mmol/L) within 48 hours post-surgery. Secondary endpoints include the occurrence of hypocalcemia at various time points post-surgery, modification of surgical procedures, intraoperative parathyroid vitality scores, and any adverse reactions to indocyanine green.

The trial is expected to run from April 2021 to December 2026. Participants will be involved in the study for a maximum treatment period of one day, with follow-up visits scheduled at day 8, month 1, and month 6 post-surgery. The inclusion visit will involve screening for eligibility, which includes patients requiring total thyroidectomy, those who have signed consent, and are covered by a social security scheme. There are no specified exclusion criteria. The end-of-study visit will assess the final outcomes and any long-term effects.

Participants may be terminated early from the study if they experience significant adverse reactions to the investigational product or if they withdraw consent. The study will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the safety and well-being of participants throughout the trial duration.

The clinical trial involves the use of **Indocyanine Green** as the experimental medication. The product, marketed under the name **INFRACYANINE 25 mg/10 mL**, is provided in the form of a powder and solvent for solution injectable, classified as a **SOLUTION FOR INJECTION**. The active substance, **Indocyanine Green**, is of chemical origin and is utilized for its diagnostic properties, specifically categorized under the ATC code **V04CX**, which denotes other diagnostic agents. The administration of this medication is conducted via injection, with a maximum daily dose of 0.5 mg/kg and a total dose not exceeding 0.5 mg/kg. The treatment period is limited to a single day. The product is not formulated for pediatric use and is not classified as an orphan drug.

In this study, the experimental group receiving **Indocyanine Green** will be compared to a control group that does not receive the experimental medication. The primary objective is to assess the incidence of albumin-corrected hypocalcemia, a condition associated with hypoparathyroidism, following total thyroidectomy. The trial does not involve any additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed by comparing the incidence of **albumin-corrected hypocalcaemia** postoperatively between two groups: one using indocyanine green and the other not using it. The primary endpoint is the occurrence of albumin-corrected hypocalcaemia (≤2 mmol/L) within 48 hours of surgery. Secondary endpoints include the occurrence of post-operative hypocalcaemia corrected by albumin at day 8, month 1, and month 6, and the modification of the surgical procedure by improving detection of the parathyroids or their vascularisation during thyroidectomy with the use of indocyanine green angiography. Additionally, the intraoperative parathyroid vitality score when using indocyanine green angiography, the occurrence of hypoPTH on days 1 and 2 post-operation (<10 ng/L), and the occurrence of mild, moderate, and profound hypocalcaemia in the 48 postoperative hours will be evaluated. The occurrence of any adverse reaction linked to the injection of indocyanine green will also be monitored.