The Longitudinal PTH-Study

Study Overview
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Brief Summary
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The main study aim is to quantify the agreement between the analytical results provided by two third generation and two second generation Parathyroid hormone (PTH) assays. The primary comparison will be performed between the second-generation PTH assayIntact PTH assay from Siemens Healthcare Diagnostics Inc. and the third-generation PTH assay biointact (1-84) from Roche Diagnostics in terms of a Bland-Altman analysis. Several studies have evaluated the correlation between various PTH assays at a single time-point, but no previous study has tested the hypothesis that longitudinal changes in PTH levels, which are important for making treatment decisions, can be monitored by several PTH assays alike. To this aim, the key secondary objective is to analyze the longitudinal variance in PTH over the course of 1 year, using each of two assays of the second and third generations, respectively. Other secondary objectives include determining changes in serum phosphate, serum calcium, fibroblast growth factor 23 (FGF23), with respect to treatment decisions. For clinical applicability of the results to be obtained here, an important goal of the present study will be not to influence treatment decisions, which will remain independent of the study investigators, at the full responsibility of the hemodialysis physicians. At every quarterly blood draw over the course of one year, the investigators will freeze the serum from 100 patients, and at the end of 4 quarters the investigators will analyze PTH-levels using the following assays: Intact Parathyroid Hormone (Advia Centaur, Siemens Healthcare), PTH-Intact (Cobas, Roche), PTH (1-84) - The agreement between the PTH assays will be analyzed at baseline, as well as at the subsequent quarterly evaluation time-points by Bland-Altman analysis and complemented by Passing-Bablok regression. The longitudinal changes in PTH will be displayed graphically and analyzed by estimating the within-patient variance across time, the between patient variance at each time-point as well as effects on the mean log-PTH level due to course of disease and therapeutic interventions from a linear mixed model.

Official Title
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Intact Versus Biointact Assays for Longitudinal Assessment of Parathyroid Hormone - The Longitudinal PTH Study

Conditions
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CKD-MBD - Chronic Kidney Disease Mineral and Bone Disorder, Secondary Hyperparathyroidism, Kidney Replacement

Intervention / Treatment
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* Diagnostic Test: One armed study, blood from each patient is analysed by four assays ( two 3rd generation and two 2nd generation assays)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients who were undergoing uninterrupted hemodialysis or hemodiafiltration at the Chronic Hemodialysis Unit of the Division of Nephrology and Dialysis, Medical University of Vienna between November 1st, 2017 and December 31st, 2018. Existence of residual blood samples from four successive quarterly routine controls Age ≥ 18 years The test result of the assay must not have any diagnostic value or therapeutic consequence for the patients included in this study. Exclusion Criteria: Death during the observational period (all patients must have lived through the 1-year period and must have all 4 quarterly blood draws performed on them). Age <18 years

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Arm<br>One armed study, blood from each patient is analysed by the following assays: Intact PTH Assay (Siemens Healthcare Diagnostics Inc); LIAISON 1-84 PTH Assay (Diasorin); PTH (1-84), biointact (Roche Diagnostics); PTH, intact (Roche Diagnostics) | Diagnostic Test: One armed study, blood from each patient is analysed by four assays ( two 3rd generation and two 2nd generation assays)<br>* Intact PTH Assay (Siemens Healthcare Diagnostics Inc); LIAISON 1-84 PTH Assay (Diasorin); PTH (1-84), biointact (Roche Diagnostics); PTH, intact (Roche Diagnostics)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal change in PTH levels measured in [pg/ml] | PTH levels as measured by the second and third generation assays | Timepoints of four consecutive quarterly routine controls per patient (month 1; month 4 ; month 8, month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal within-patient change of PTH levels in [pg/ml] | Longitudinal within-patient variance of PTH over the course of 1 year, using each of two assays of the second and third generations, respectively. | Timepoints of four consecutive quarterly routine controls per patient (month 1; month 4 ; month 8, month 12) | 
| Serum Calcium levels | Serum Calcium levels | Timepoints of four consecutive quarterly routine controls per patient (month 1; month 4 ; month 8, month 12) | 
| Serum Phosphate levels | Serum Phosphate levels as measured by quarterly routine controls | Timepoints of four consecutive quarterly routine controls per patient (month 1; month 4 ; month 8, month 12) | 
| Fibroblast growth factor 23 (FGF23 | Fibroblast growth factor 23 (FGF23) as measured in quarterly routine controls | Timepoints of four consecutive quarterly routine controls per patient (month 1; month 4 ; month 8, month 12) |