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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperparathyroidism, Secondary
• Intervention / Treatment: Procedure: Subtotal Parathyroidectomy; Procedure: Total Parathyroidectomy + 45 autografts; Procedure: Total Parathyroidectomy + 90 autografts

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil
      • University of Sao Paulo General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subtotal Parathyroidectomy; 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; 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.
Active Comparator: Total Parathyroidectomy + 45 autografts; 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; 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.
Experimental: Total Parathyroidectomy + 90 autografts; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Sergio S Arap, M.D., University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• Filho WA, van der Plas WY, Brescia MDG, Nascimento CP Jr, Goldenstein PT, Neto LMM, Arap SS, Custodio MR, Bueno RO, Moyses RMA, Jorgetti V, Kruijf S, Montenegro FLM. Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial. Surgery. 2018 Nov;164(5):978-985. doi: 10.1016/j.surg.2018.06.032. Epub 2018 Aug 3. Erratum In: Surgery. 2019 Feb;165(2):497.
• Albuquerque RFC, Carbonara CEM, Martin RCT, Dos Reis LM, do Nascimento CP Junior, Arap SS, Moyses RMA, Jorgetti V, Montenegro FLM, de Oliveira RB. Parathyroidectomy in patients with chronic kidney disease: Impacts of different techniques on the biochemical and clinical evolution of secondary hyperparathyroidism. Surgery. 2018 Feb;163(2):381-387. doi: 10.1016/j.surg.2017.09.005. Epub 2017 Nov 13.
• Silveira AA, Brescia MDG, do Nascimento CP Jr, Arap SS, Montenegro FLM. Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism. Surgery. 2020 Dec;168(6):1079-1085. doi: 10.1016/j.surg.2020.06.043. Epub 2020 Aug 15.
• Silveira AA, Brescia MDG, Nascimento CPD Jr, Arap SS, Montenegro FLM. Delayed sampling of intraoperative parathormone may be unnecessary during parathyroidectomy in kidney-transplanted and dialysis patients. J Bras Nefrol. 2021 Apr-Jun;43(2):228-235. doi: 10.1590/2175-8239-JBN-2020-0108.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: May 18, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Renal Insufficiency, Chronic; Parathyroidectomy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hyperparathyroidism; Hyperparathyroidism, Secondary
• Other Study ID Numbers: CAAE 00828412.8.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No