Hematologic DiseasesPROTECTNCT02329808
Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics
An observational study of Hematologic Diseases and Oncology Problem, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Hematologic Diseases, Oncology Problem, Kidney Diseases
- What is being tested?
- blood drawing
- Type of treatment
- Surgery or procedure
- How many people
- 93 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2015to 3 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric hemato-oncology and primariy immunodeficient patients and pediatric renal transplantation patients.
Who may be able to join
- 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
Who cannot join
- Parents and/or patients are not able to understand the Dutch language
Trial locations and contacts
1 site in 1 country.
About this study
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).
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.
Read the 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.
- Being tested
- blood drawing
- Keywords
- TDM, dried blood spot, immunosuppressive, antifungal
- Medical subject headings
- Hematologic Diseases, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood drawingProcedure or surgery
The association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolic acid | Patients treated for their regular patient care with mycophenolic acid. Receives: Procedure: blood drawing | |
| Cyclosporin | Patients treated for their regular patient care with cyclosporin. Receives: Procedure: blood drawing | |
| Tacrolimus | Patients treated for their regular patient care with tacrolimus. Receives: Procedure: blood drawing | |
| Sirolimus | Patients treated for their regular patient care with sirolimus. Receives: Procedure: blood drawing | |
| Everolimus | Patients treated for their regular patient care with everolimus. Receives: Procedure: blood drawing | |
| Voriconazole | Patients treated for their regular patient care with voriconazole. Receives: Procedure: blood drawing | |
| Posaconazole | Patients treated for their regular patient care with posaconazole. Receives: Procedure: blood drawing | |
| Itraconazole+metabolite | Patients treated for their regular patient care with itraconazole. Receives: Procedure: blood drawing | |
| Fluconazole | Patients treated for their regular patient care with fluconazole. Receives: Procedure: blood drawing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: predose, 2 samples postdose, max 6 hours post dose
Secondary outcomes (3)
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.
Measured: 1 day
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.
Measured: 2 years
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).
Measured: 6h period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2015 (estimated)
- Study startJun 2015
- Primary completion3 Dec 2021
- Study completion3 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor
- Investigators
- Roger Bruggemann, PharmD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02329808
- Sponsor's protocol ID
- UMCN-AKF 14.02
- Acronym
- PROTECT
- Status last verified
- May 2022
- First submitted
- 19 Dec 2014
- Last updated
- 10 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT02329808
- Acronym / sponsor ID
- PROTECT / UMCN-AKF 14.02
- Keywords
- TDM, dried blood spot, immunosuppressive, antifungal
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Jun 2015 (actual)
- Primary completion
- 3 Dec 2021 (actual)
- Study completion
- 3 Dec 2021 (actual)
- First posted
- 1 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Mycophenolic acid | – | Procedure: blood drawingPatients treated for their regular patient care with mycophenolic acid. |
| Cyclosporin | – | Procedure: blood drawingPatients treated for their regular patient care with cyclosporin. |
| Tacrolimus | – | Procedure: blood drawingPatients treated for their regular patient care with tacrolimus. |
| Sirolimus | – | Procedure: blood drawingPatients treated for their regular patient care with sirolimus. |
| Everolimus | – | Procedure: blood drawingPatients treated for their regular patient care with everolimus. |
| Voriconazole | – | Procedure: blood drawingPatients treated for their regular patient care with voriconazole. |
| Posaconazole | – | Procedure: blood drawingPatients treated for their regular patient care with posaconazole. |
| Itraconazole+metabolite | – | Procedure: blood drawingPatients treated for their regular patient care with itraconazole. |
| Fluconazole | – | Procedure: blood drawingPatients treated for their regular patient care with fluconazole. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Pediatric hemato-oncology and primariy immunodeficient patients and pediatric renal transplantation patients.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (1 listed)
- Parents and/or patients are not able to understand the Dutch language
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood drawingThe association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways. | Procedure or surgery | Cyclosporin, Everolimus, Fluconazole, Itraconazole+metabolite, Mycophenolic acid, Posaconazole, Sirolimus, Tacrolimus, Voriconazole |
Primary outcome
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.
3 secondary outcomes
Questionnaire
Time frame: 1 day
costs
Time frame: 2 years
Area under the curve
Time frame: 6h period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger Bruggemann, PharmD PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematologic Diseases and Oncology Problem, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
drug concentration (time frame: predose, 2 samples postdose, max 6 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.