Calcium+Calcitriol Versus PTH for the Prevention of Hypocalcemia in Thyroidectomy. Randomized Clinical Trial

Study Overview
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Brief Summary
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The objective of this study is to compare the frequency of post-thyroidectomy symptomatic and biochemical hypocalcaemia between the strategy of routine prophylactic calcium + calcitriol vs the administration of calcium guided by PTH values.

Detailed Description
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Postoperative hypocalcaemia is the most common complication that occurs in patients undergoing total thyroidectomy 1, with a frequency between 15 and 30%. 1-3 In the vast majority of cases, this complication is transitory, and only 1-3% manifest definitively. 4.5 Hypocalcemia is produced by surgical manipulation of the parathyroid glands, where their vascularization may be compromised, by stunning, or by inadvertent removal of the glands during thyroidectomy. 3,4 Other risk factors that have been associated include bilateral resection, inflammatory disease, and parathyroid reimplantation.1,6 Despite minimal manipulation during the surgical procedure, episodes of postoperative hypocalcemia continue to occur. To reduce the frequency of appearance and obtain symptomatic relief in the patient, several preventive strategies have been developed, 4,7-9 among which are the postoperative prophylactic administration of calcium + calcitriol 5,9 and the postoperative measurement of parathyroid hormone ( PTH) as a reference for oral calcium administration. 4,10 These strategies differ in the frequency of adverse events and cost. To date, these two interventions have not been directly compared in a clinical trial to determine which of them offers greater effectiveness and fewer adverse events and costs, and their use is made according to the individual preferences of the surgeon. A randomized clinical trial would offer information of high methodological quality for the standardization of conduct. Research Question In a postoperative total thyroidectomy patient, is the calcium + calcitriol administration strategy based on postoperative PTH measurement superior to the routine prophylactic administration of calcium + calcitriol to reduce the frequency of symptomatic and postoperative biochemical hypocalcaemia? Justification Postoperative hypocalcaemia is a condition that occurs in up to a third of postoperative total thyroidectomy patients. Hypocalcaemia worsens the clinical condition of the patient, implies prolongations of the hospital stay, readmissions and use of medications. 2,3,6 In addition to an adequate surgical technique, its prevention involves pharmacological interventions and diagnostic tests. Among the alternatives currently used is the prophylactic administration of calcium and calcitriol for two weeks. 11 Despite being a cheap and safe strategy, it has uncomfortable side effects for the patient such as constipation, epigastric pain, metallic taste, loss of appetite and mood changes. 12,13 Due to this, several authors have proposed the measurement of calcium or PTH in the immediate postoperative period as a reference to decide the need for oral administration of calcium and calcitriol, thus avoiding unnecessary use in patients with normal values. 2,4,8,10,11 Theoretically, a measurement of PTH >10 pg/ml in the postoperative period would allow predicting patients who are at greater risk of developing hypocalcaemia than those who are not and can be discharged without taking calcium + calcitriol, but studies are very heterogeneous and difficult to compare with each other. 2.14 Recently, a meta-analysis evaluated the strategy of administration of calcium + calcitriol vs calcium measurement with advantages for the first 10, but there are few clinical trials that compare this strategy with postoperative PTH measurement. 14 Because this surgical group performs outpatient management after thyroidectomy, defining which of the two strategies offers greater effectiveness and a better profile of adverse events is of the utmost importance, as it would allow making general recommendations and adjusting current institutional protocols. On the other hand, the result of this trial would be a potential source of information to evaluate the cost-effectiveness of interventions in the future. Aim: To compare the frequency of post-thyroidectomy symptomatic and biochemical hypocalcaemia between the strategy of routine prophylactic calcium + calcitriol vs the administration of calcium guided by PTH values.

Official Title
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Comparison of Routine Prophylactic Calcium + Calcitriol and Selective Use Based on PTH for the Prevention of Postoperative Hypocalcemia in Patients With Total Thyroidectomy. Randomized Clinical Trial

Conditions
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Thyroid Cancer, Goiter, Thyroiditis, Hyperthyroidism

Intervention / Treatment
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* Diagnostic Test: calcium correction according to PTH levels
* Drug: routine postoperative calcium and calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients undergoing total thyroidectomy who meet the following criteria: Patients over 18 years of age, Benign (goiter, thyroiditis, hyperthyroidism) or malignant (carcinoma) diagnosis, Patients who agree to participate in the study and sign the informed consent. Exclusion Criteria: - Patients with parathyroid surgery in conjunction with thyroidectomy, Patients with prior parathyroid disease for other causes (hyperparathyroidism primary or secondary to kidney disease, etc.), Patients with anaplastic carcinoma or lymphoma, Patients undergoing total thyroidectomy for causes other than thyroid disease such as, for example, total laryngectomy or pharyngo-laryngectomy that, due to margins or direct extension, require thyroidectomy. , Altered cognitive state that interfered or made the evaluation impossible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, parallel, multicenter stratified clinical trial with 1:1 allocation.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: calcium correction according to PTH levels<br>A PTH blood test will be performed 4 hours post-thyroidectomy. | Diagnostic Test: calcium correction according to PTH levels<br>* A PTH blood test will be performed 4 hours post-thyroidectomy. If the PTH result is >15 pg/mL, the patient will be discharged without calcium intake; if PTH < 15 pg/mL, start a dose of 1200 mg Calcium carbonate every 8 hours + 0.25 mcg of calcitriol every 12 hours orally for 15 days<br>* Other names: PTH;|
| Active Comparator: routine postoperative calcium and calcitriol<br>The patient will receive Calcium carbonate + calcitriol | Drug: routine postoperative calcium and calcitriol<br>* The patient will receive a dose of 1,200 mg Calcium carbonate every 8 hours + 0.25 mcg of calcitriol every 12 hours orally for 15 days, starting on the same day as the intervention.<br>* Other names: calcium carbonate, calcitriol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| symptomatic hypocalcaemia | The presence of symptomatic hypocalcaemia in the postoperative period of thyroidectomy defined according to the scale proposed by Wilde et al. (hypoparathyroid patient questionnaire HPQ) Min value 0 Max value 60 Higher scores represent worst symptoms | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical hypocalcemia | Biochemical hypocalcemia defined as serum calcium < 8 mg/dL or PTH < 15 | 48 hours and 15 days postoperatively | 
| Adverse events of the medication | Adverse events of the medication (calcium+calcitriol) included in the scale of Wilde et al. | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thyroidectomy, hypocalcemia, randomized clinical trial