Subtotal Parathyroidectomy or Total Parathyroidectomy With Autograft in Chronic Kidney Disease Patients Under Dialysis

Study Overview
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Brief Summary
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This study evaluates the metabolic and clinical results of two well recognized and accepted surgical techniques in the management of severe hyperparathyroidism in patients under regular dialysis treatment.

Detailed Description
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Prospective randomized trial in the surgical management of severe hyperparathyroidism of chronic kidney disease stage V under dialysis. Patients will be randomized and they will be submitted to subtotal parathyroidectomy or total parathyroidectomy with immediate heterotopic autograft of 45 or 90 fragments of parathyroid tissue.

Official Title
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Randomized Clinical Trial of Subtotal Parathyroidectomy or Total Parathyroidectomy With Immediate Heterotopic Autograft in Chronic Renal Disease Patients Stage V Under Dialysis

Conditions
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Hyperparathyroidism, Secondary

Intervention / Treatment
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* Procedure: Subtotal Parathyroidectomy
* Procedure: Total Parathyroidectomy + 45 autografts
* Procedure: Total Parathyroidectomy + 90 autografts


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage V Chronic Kidney Disease patients under regular dialysis treatment with severe hyperparathyroidism requiring parathyroidectomy Exclusion Criteria: patients refusing to participate in the study (they will receive standard surgery), patients unable to attend regular follow up consultations, patients with a successful kidney transplant at the moment of parathyroidectomy, patients submitted to any previous surgery of the thyroid or parathyroid, patients with chronic kidney disease but not under dialysis
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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subtotal Parathyroidectomy<br>Patients will be submitted to subtotal parathyroidectomy. The intention is to leave a parathyroid remanent equivalent to two normal parathyroid glands in situ. The type of the operation is the intervention. No drugs or devices are tested. | Procedure: Subtotal Parathyroidectomy<br>* Subtotal parathyroid resection leaving the estimated mass of two normal parathyroid glands in situ. The type of operation is the intervention. No new device or drug is involved.<br>|
| Active Comparator: Total Parathyroidectomy + 45 autografts<br>Patients will be submitted to a total parathyroidectomy and 45 fragments of parathyroid tissue are grafted in the forearm. This is the current standard treatment at the institution for severe secondary hyperparathyroidism.The type of operation is the intervention itself. No new device or drug is involved. | Procedure: Total Parathyroidectomy + 45 autografts<br>* Immediate autograft of 45 fragments of parathyroid tissue, after a total parathyroidectomy.This type of operation is the standard intervention at the institution at the moment. No new device or drug is involved.<br>|
| Experimental: Total Parathyroidectomy + 90 autografts<br>Patients will be submitted to a total parathyroidectomy and 90 fragments of parathyroid tissue are grafted in the forearm. The type of operation is the intervention. No new device or drug is involved. . | Procedure: Total Parathyroidectomy + 90 autografts<br>* Immediate autograft of 90 fragments of parathyroid tissue, after a total parathyroidectomy.The type of operation is the intervention. No new device or drug is involved.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Five years survival after parathyroidectomy in an intention to treat analysis | From the time of the operation until 5 years after intervention or death if it occurs before 5 years of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic Outcome 1: Serum Calcium (mg/dL) | postoperative calcium levels. Below, Above or in the normal range for the method. Analysis will include samples taken close to 1, 3, 6, 12, 24, 36, 48 and 60 months after the operation. | 1 to 60 months after intervention, Samples are taken according to regular follow up | 
| Metabolic Outcome 2 : Serum Phosphorus (mg/dL) | postoperative phosphorus levels. Below, above or the normal range for the method employed. Analysis will include samples taken close to 1, 3, 6, 12, 24, 36, 48 and 60 months after the operation. | 1 to 60 months after intervention, Samples are taken according to regular follow up | 
| Metabolic Outcome 3: Serum Alkaline Phosphatase (IU) | postoperative alkaline phosphatase levels. Above or in the normal range, according to the method in use. Analysis will include samples taken close to 1, 3, 6, 12, 24, 36, 48 and 60 months after the operation. | 1 to 60 months after intervention, Samples are taken according to regular follow up | 
| Metabolic Outcome 4: Serum Parathormone (pg/mL) | postoperative parathormone levels. Below, Above or in the target levels proposed by the National Kidney Foundation, and by the Kidney Disease Improving Global Outcomes (KDIGO). Analysis will include samples taken close to 1, 3, 6, 12, 24, 36, 48 and 60 months after the operation. | 1 to 60 months after intervention, Samples are taken according to regular follow up | 
| Drug Requirement 1: Elemental Calcium Intake (g/day) | The calcium supplement intake (in grams of elemental calcium per day) of the patients after the intervention. Analysis will include first week, then 1, 3, 6, 12, 24,36, 48, 60 months after the intervention. | 1 to 60 months after intervention, according to the dose prescibed in different periods. | 
| Drug Requirement 2 Calcitriol intake (micrograms/day) | calcitriol or other vitamin D analogue intake (in micrograms per day) after the intervention. Analysis will include first week, then 1, 3, 6, 12, 24,36, 48, 60 months after the intervention. | 1 to 60 months after intervention, according to the dose prescibed in different periods | 
| Drug Requirement 3: Sevelamer (mg/day) | The quantity of phosphorus binding drugs, in special Sevelamer prescribed in milligrams after the intervention. Analysis will include 1, 3, 6, 12, 24,36, 48, 60 months after the operation. | 1 to 60 months after intervention, according to the dose prescibed in different periods | 
| Drug Requirement 4: Calcimimetics (mg/day) | The amount of Calcimimetics, in special Cinacalcet im milligrams per day prescribed after the intervention. Analysis will include 1, 3, 6, 12, 24,36, 48, 60 months after the intervention. | 1 to 60 months after intervention, according to the dose prescibed in different periods | 
| Clinical Outcome 1: Bone Pain in the VAS | Bone pain measured by the Visual Analogic Pain Scale up to one week before the intervention and up to one week after the procedure, and then at regular follow up. Analysis will concentrate on preoperative (up to one week before), postoperative up to one week, 6,12, 24, 36, 48 and 60 months after the intervention. | Pre-operative (up to one week before the procedure) until 60 months after intervention | 
| Clinical Outcome 2: Postoperative Skeletal Disease (Fractures/Brown tumor) | skeletal disease is defined as the occurrence of a fracture or the developement brown tumor (osteoclastomas) after the intervention, detected clinically or by any clinically oriented radiography ordered by the attending physician in routine follow up or in any emergency setting. | 1 to 60 months after intervention | 
| Clinical Outcome 3: Quality of Life in the SF-36 Questionnaire | quality of life up to one week before the intervention and after the operation at one week, 6 , 12, 24, 36, 48 and 60 months, measured by the Short form 36 questionnaire (SF-36) validated to the cultural and language of the country. | Preoperative (up to three days before the intervention) and until 60 months after intervention | 
| Clinical Outcome 4: Additional Operation (Reoperation in Recurrent/Persistent Disease) | the necessity of reoperative procedures due to recurrence or persistence of severe hyperparathyroidism, as defined by the attending physician during regular follow up | 1 to 60 months after intervention | 
| Morbidity of the surgical procedures | After any interventions (initial operation or reoperative interventions necessary in the follow up), it will be actively searched for the occurrence of dysphonia (and its cause according to laryngoscopy), wound infection (clinical signs as red skin, pain, secretion, fever and laboratory evidence), and neck haematoma (large neck blood clots requiring operation) | intra-operative to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parathyroidectomy, Renal Insufficiency, Chronic