Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics

Kidney Diseases Clinical Trial

— PROTECT  

Official title:

Clinical Validation of a Dried Blood Spot (DBS) Method for the Analysis of Immunosuppressive and Antifungal Drugs in Pediatric Patients (Part of the PROTECT Study).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02329808
• Other study ID #: UMCN-AKF 14.02
• Status: Completed
• Start date: June 2015
• Est. completion date: December 3, 2021

Study information

• Verified date: May 2022
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a clincial validation study of a dried blood spot (DBS) method for the analysis of immunosuppressive and antifungal agents currently subject of therapeutic drug monitoring (TDM) in a pediatric population.

The primary goal is to clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy goals include feasibility of the finger prick DBS method in the target population, to design an inventory of costs that will be incurred in future health-economic analyses and to construct a population PK model based on the available data collected for the primariy goal.

Description:

Therapeutic drug monitoring (TDM) offers the possibility to individualize and improve a patient's pharmacological treatment, based on the measurement of drug concentrations in biological samples. Conventionally, TDM is performed with blood or plasma obtained by venous blood sampling. This method is associated with several challenges such as i) the need for the patient to travel to the hospital or health center; ii) special conditions for sample transport to guarantee stability of the analyte and to decrease the biohazard risk; iii) sampling times not always representing the preferable peak or trough concentrations; iv) the method being invasive and v) delay of the outcome of the analyses with regard to the outpatient visit.

The Dried Blood Spot (DBS) may offer a solution for all these challenges. DBS is thought to offer benefits over plasma venous sampling for TDM. The main purpose of the PROTECT (Personalized treatment of immunosuppressive and antifungal drugs through continuous home based monitoring with Dried Blood Spot sampling techniques in pediatric patients) study is to improve therapeutic management and patient participation in pediatric patients treated with antifungal and immunosuppressive agents. PROTECT is mainly financed by a ZonMW grant 'Goed Gebruik Geneesmiddelen'.

Four patient organizations are actively involved in the PROTECT study.

Objective of the study:

Primairy To clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy

• Feasibility of the novel finger prick DBS method in the pediatric population will be assessed. This includes scoring of relevant characteristics (attributes) of blood drawing methods for TDM, evaluation of the experience and attitude of both patients and parents regarding finger prick DBS sampling and evaluation of the understanding of the written instructions provided for performing the finger prick at home. The data obtained in this validation study will be used for the implementation of the DBS in therapeutic drug monitoring (TDM) being a less invasive procedure, and as a base for a discrete choice-experiment as part of the HTA.

• To design an inventory of types of costs that will be incurred in the process of DBS-based and conventional TDM as a preparation step for later health economic analysis.

• Data from this study will be used to construct a population pharmacokinetic model to optimize dosing and design new guidelines.

This is an observational mono-centre study in which DBS sampling is compared with conventional sampling for TDM in a steady state situation.

Clearly, information on feasibility of DBS sampling in children and on costs relevant to DBS sampling in children can only be obtained through actual sampling in children.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: December 3, 2021
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• Patients aged between 2 and 18 years

• Admitted to the Radboudumc pediatric ward

• Having a venous catheter

• Treated with at least 1 of the 9 drugs of interest

• The drug concentration being at steady state

• Signed informed consent

Exclusion Criteria:

• Parents and/or patients are not able to understand the Dutch language

Related Conditions & MeSH terms

• Hematologic Diseases
• Kidney Diseases
• Oncology Problem
• Transplantation Infection

Intervention

Procedure:
• blood drawing
The association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways.

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	drug concentration	The outcome measure is a composite of several blood concentrations, obtained by three individual blood drawing moments per patient. The related endpoint is the evaluation of the association between the concentration obtained by venous sampling and the concentration obtained by means of DBS sampling. The predictive performance of the DBS method as a measure for the venous concentration will be evaluated.	predose, 2 samples postdose, max 6 hours post dose
Secondary	Questionnaire	The related endpoint is the response to a questionnaire. Results will be used to prepare implementation of the novel method for home-based monitoring as well as to prepare a HTA analysis.	1 day
Secondary	costs	Costs of blood drawing methods will be collected.The cost types will function as a basis for future HTA analysis of this novel sampling method compared to conventional venous sampling.	2 years
Secondary	Area under the curve	Blood concentrations will be used to calculate the area under the concentration time curve (AUC). The outcome measure will be a composite of population estimates of the pharmacokinetic parameters AUC, maximal concentration (Cmax), time to maximal concentration (Tmax), clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2).	6h period