The Longitudinal PTH-Study

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

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 assay"Intact 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.

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism; CKD-MBD - Chronic Kidney Disease Mineral and Bone Disorder; Kidney Replacement
• Intervention / Treatment: Diagnostic test: One armed study, blood from each patient is analysed by four assays ( two 3rd generation and two 2nd generation assays)

• Study Type: Observational
• Enrollment (Actual): 132

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

132 hemodialysis patients at a single center

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Arm; 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); Intact PTH Assay (Siemens Healthcare Diagnostics Inc); LIAISON 1-84 PTH Assay (Diasorin); PTH (1-84), biointact (Roche Diagnostics); PTH, intact (Roche Diagnostics)

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Manfred Hecking, M.D., Medical University of Vienna, Department of Nephrology and Dialysis

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): August 7, 2019

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: March 12, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Nutrition Disorders; Musculoskeletal Diseases; Parathyroid Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Rickets; Vitamin D Deficiency; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Bone Diseases; Hyperparathyroidism, Secondary; Chronic Kidney Disease-Mineral and Bone Disorder
• Other Study ID Numbers: The Longitudinal PTH-Study

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