Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02329808
Recruitment Status : Recruiting
First Posted : January 1, 2015
Last Update Posted : July 13, 2020
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Radboud University

Brief 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.


Condition or disease Intervention/treatment
Hematologic Diseases Oncology Problem Kidney Diseases Transplantation Infection Procedure: blood drawing

Detailed 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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 126 participants
Observational Model: Cohort
Time Perspective: Prospective
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).
Actual Study Start Date : June 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rashes

Group/Cohort Intervention/treatment
Mycophenolic acid
Patients treated for their regular patient care with mycophenolic acid.
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.

Cyclosporin
Patients treated for their regular patient care with cyclosporin.
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.

Tacrolimus
Patients treated for their regular patient care with tacrolimus.
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.

Sirolimus
Patients treated for their regular patient care with sirolimus.
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.

Everolimus
Patients treated for their regular patient care with everolimus.
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.

Voriconazole
Patients treated for their regular patient care with voriconazole.
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.

Posaconazole
Patients treated for their regular patient care with posaconazole.
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.

Itraconazole+metabolite
Patients treated for their regular patient care with itraconazole.
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.

Fluconazole
Patients treated for their regular patient care with fluconazole.
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.




Primary Outcome Measures :
  1. drug concentration [ Time Frame: predose, 2 samples postdose, max 6 hours post dose ]
    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.


Secondary Outcome Measures :
  1. Questionnaire [ Time Frame: 1 day ]
    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.

  2. costs [ Time Frame: 2 years ]
    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.

  3. Area under the curve [ Time Frame: 6h period ]
    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).


Biospecimen Retention:   Samples With DNA
Plasma without DNA, blood with DNA and dried blood spot (with DNA)


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Pediatric hemato-oncology and primariy immunodeficient patients and pediatric renal transplantation patients.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02329808


Contacts
Layout table for location contacts
Contact: Roger Brüggemann 0031243616405 roger.bruggemann@radboudumc.nl
Contact: Lisa Martial 0031243616405 lisa.martial@radboudumc.nl

Locations
Layout table for location information
Netherlands
Radboud University Medical Center Recruiting
Nijmegen, Gelderland, Netherlands
Contact: Roger Brüggemann, PharmD PhD       roger.bruggemann@radboudumc.nl   
Contact: Lisa Martial, PharmD       lisa.martial@radboudumc.nl   
Sub-Investigator: Maroeska Te Loo         
Sub-Investigator: Michiel Schreuder         
Sub-Investigator: Stefanie Henriet         
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Roger Bruggemann, PharmD PhD Radboud University
Layout table for additonal information
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02329808    
Other Study ID Numbers: UMCN-AKF 14.02
First Posted: January 1, 2015    Key Record Dates
Last Update Posted: July 13, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Radboud University:
TDM
dried blood spot
immunosuppressive
antifungal
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Hematologic Diseases
Urologic Diseases