Evaluation of Preoperative Cholecalciferol Supplementation on Post-Thyroidectomy Hypocalcemia Incidence in Patients Undergoing Total Thyroidectomy

The primary objective of this study is the **assessment** of the effect of pre-operative **cholecalciferol** supplementation on the occurrence of post-operative **hypocalcemia** following total **thyroidectomy**. This is clinically relevant as transient post-operative hypocalcemia is a common complication of thyroidectomy, leading to patient discomfort, prolonged hospital stays, and increased healthcare costs. By evaluating the impact of cholecalciferol, a form of vitamin D, the study aims to determine if pre-operative supplementation can mitigate these adverse outcomes.

Secondary objectives include:

• Comparing the length of hospital stay and readmissions during follow-up between the treatment and no-treatment groups.
• Evaluating the severity of hypocalcemia in both groups.
• Assessing the effect of supplementation on vitamin D deficiency.
• Investigating parathyroid activity.
• Determining the prevalence of definitive hypocalcemia.
• Examining the effect of vitamin D supplementation on the occurrence of hypocalcemia in risk groups, such as those with hyperthyroidism, cancer, or undergoing dissection associated with thyroidectomy.

The clinical trial involves participants who are undergoing a **total thyroidectomy** for any indication. The study population includes both male and female subjects aged 18 years and older. Participants are required to have an affiliation with the social security system and must provide written informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The study aims to assess the effect of pre-operative **cholecalciferol** supplementation on the occurrence of post-operative hypocalcemia. Participants' general health status, lifestyle considerations such as diet and physical activity, and specific habits are not detailed in the provided data.

The clinical trial is designed to assess the effect of pre-operative **cholecalciferol** supplementation on the occurrence of post-operative hypocalcemia following total thyroidectomy. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span from June 2021 to March 2026, with participant involvement lasting approximately 15 days post-surgery. The primary endpoint is the measurement of serum and/or clinical hypocalcemia, defined by specific clinical signs and serum calcium levels. Secondary endpoints include the duration of initial hospitalization, severity and duration of hypocalcemia symptoms, vitamin D levels, and parathyroid activity.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), planned total thyroidectomy, and informed consent. Follow-up visits will occur post-operatively to monitor calcium levels, adverse events, and other relevant clinical parameters. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and collecting data on any long-term effects. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The trial aims to provide insights into the potential benefits of cholecalciferol supplementation in managing post-thyroidectomy hypocalcemia, thereby improving patient outcomes and reducing healthcare costs associated with prolonged hospital stays.

The clinical trial involves the administration of **UVEDOSE 100 000 UI**, an **oral solution** containing the active substance **colecalciferol**. This pharmaceutical form is a solution buvable en ampoule, designed for oral use. The medication is produced by Laboratoires Crinex and is authorized under the marketing authorization number NL15608-3400933222185. The maximum daily dose and total dose amount for this trial is 100,000 IU, administered as a single dose. The treatment period is limited to one day, and the trial aims to explore new indications for this existing product, which already holds marketing authorization. The primary objective is to assess the effect of pre-operative cholecalciferol supplementation on the occurrence of post-operative hypocalcemia following total thyroidectomy.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the administration of the experimental medication, UVEDOSE 100 000 UI. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. The administration route is strictly oral, and the chemical origin of the active substance is confirmed. The trial is conducted under strict compliance with regulatory standards to ensure the safety and efficacy of the treatment being evaluated.

The efficacy of the clinical trial will be assessed by evaluating the effect of pre-operative **cholecalciferol** supplementation on the occurrence of post-operative hypocalcemia following total thyroidectomy. The primary endpoint for efficacy assessment is the measurement of the occurrence of serum and/or clinical hypocalcemia. Serum hypocalcemia is defined by a level of calcemia, corrected for albuminemia, of less than 2.00 mmol/L. Clinical hypocalcemia is identified by the appearance of signs such as Chvostek's sign, Trousseau's sign, and paresthesias of the extremities and perioral region, observed between surgery and day 15 post-operation.

Secondary endpoints include the duration of initial hospitalization, the collection of adverse events, and the number of readmissions. The severity of hypocalcemia will be measured by a calcemia level corrected for albuminemia of less than 1.90 mmol/L and/or the use of intravenous calcium gluconate within the first 15 post-operative days. The duration of hypocalcemia symptoms will also be measured during the first 15 days post-operation. Vitamin D deficiency will be assessed by comparing the initial 25OHD value at the inclusion visit to the 25OHD value on the day of the operation. Parathyroid activity will be evaluated by measuring parathormone (PTH) levels, with hypoparathyroidism defined by PTH levels below 15 ng/L. Data collection will include the number of adverse events, serum calcium levels, and the number of definitive hypocalcemia cases in each group.