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A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02372357
Recruitment Status : Completed
First Posted : February 26, 2015
Last Update Posted : March 3, 2015
Sponsor:
Collaborator:
Institutul Clinic Fundeni
Information provided by (Responsible Party):
Ap.r Kim Vanstraelen, Universitaire Ziekenhuizen Leuven

Tracking Information
First Submitted Date  ICMJE February 6, 2015
First Posted Date  ICMJE February 26, 2015
Last Update Posted Date March 3, 2015
Study Start Date  ICMJE February 2012
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
pharmacokinetic parameters of posaconazole [ Time Frame: One day at steady state posaconazole treatment ]
9 blood samples are taken during one day at steady state posaconazole plasma concentrations. The following pharmacokinetic parameters will be calculated using non-compartmental pharmacokinetic analysis: Cmax, Cmin, Tmax, Area Under the Curve during 1 dosing interval and over 24 hours, Clearance, Distribution volume, Halflife.
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
pharmacokinetic parameters of posaconazole in children of 13 years or younger are measured using non-compartmental analysis. [ Time Frame: One day at steady state posaconazole treatment ]
9 blood samples are taken during one day at steady state posaconazole plasma concentrations. The following pharmacokinetic parameters will be calculated using non-compartmental pharmacokinetic analysis: Cmax, Cmin, Tmax, Area Under the Curve during 1 dosing interval and over 24 hours, Clearance, Distribution volume, Halflife.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
  • Safety of posaconazole, focussing on nausea, vomiting and liver function abnormalities (according to the Common Terminology Criteria for Adverse Events (CTCAE classification). [ Time Frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks ]
    Patients receiving posaconazole prophylactically are closely monitored for adverse events possibly related to the drug. They are clinically monitored for nausea, vomiting and diarrhea. Liver function abnormalities are scored according to the CTCAE classification.
  • Efficacy: patients are monitored for breakthrough infections according the the European Organisation for Research and Treatment of Cancer- Mycoses Study Group (EORTC-MSG) criteria. [ Time Frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks ]
    Patients receiving posaconazole prophylactically are closely monitored for the presence of an invasive fungal infection. Patients are closely followed in case an invasive fungal infection is suspected: Fever is monitored, radiography is performed and galactomannan is measured frequently. Invasive fungal infections are categorized according to the revised EORTC-MSG criteria
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
  • Safety of posaconazole in children of 13 years or younger, focussing on nausea, vomiting and liver function abnormalities (according to the Common Terminology Criteria for Adverse Events (CTCAE classification). [ Time Frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks ]
    Patients receiving posaconazole prophylactically are closely monitored for adverse events possibly related to the drug. They are clinically monitored for nausea, vomiting and diarrhea. Liver function abnormalities are scored according to the CTCAE classification.
  • Efficacy: patients are monitored for breakthrough infections according the the European Organisation for Research and Treatment of Cancer- Mycoses Study Group (EORTC-MSG) criteria. [ Time Frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks ]
    Patients receiving posaconazole prophylactically are closely monitored for the presence of an invasive fungal infection. Patients are closely followed in case an invasive fungal infection is suspected: Fever is monitored, radiography is performed and galactomannan is measured frequently. Invasive fungal infections are categorized according to the revised EORTC-MSG criteria
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area
Official Title  ICMJE A New Dosing Regimen for Posaconazole Prophylaxis in Children Based in Body Surface Area
Brief Summary A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
Detailed Description

Invasive fungal infections (IFI), especially candidiasis and aspergillosis, are a serious threat to immunocompromised pediatric patients. Because diagnosis of IFI in pediatric patients is difficult, due to the lack of specific clinical and radiological signs and the low sensitivity of blood cultures, antifungal prophylaxis would largely optimize management of IFI in this setting. However, antifungal prophylaxis remains a matter of debate, as no clear consensus has yet been reached about the optimal drug. Very limited pediatric data are available, and current guidelines are mainly based on extrapolation of adult data. Fluconazole remains the drug of choice in many centers, despite its non-mould active spectrum. Itraconazole, liposomal amphotericin B and nebulized lipid-formulations of amphotericin B are often used off-label, although neither their pharmacokinetics (PK), nor their efficacy and safety have been documented in a proper way. Voriconazole is registered for children older than 2 years of age, mainly in the treatment setting. Moreover, its extremely variable PK profile, uncertainty about adequate exposure and risk for hepatotoxicity and neurotoxicity do not favor the use of voriconazole in this setting. Finally, micafungin only has low recommendation in the prophylactic setting, due to the possible risk of liver tumours.

Posaconazole would be the ideal antifungal drug to be used prophylactically in children for many reasons. It has a broad spectrum of activity, including emerging moulds like Aspergillus spp. and Zygomycetes. It has shown to be superior over fluconazole and itraconazole in preventing IFI in adults and it has a favorable safety profile, with nausea and vomiting being the most frequently encountered adverse events. However, lack of pharmacokinetic (PK) data in children younger than 13 years of age, results in only a marginal recommendation in current guidelines [8]. Little information is available about the correct dosing regimen of the available oral suspension in young pediatric patients, and similar to what is observed in adults, often very low posaconazole plasma concentrations (PPCs) are being measured. Therefore, therapeutic drug monitoring (TDM) is recommended to reach adequate PPCs above 0.5mg/L or 0.7 mg/L followed by increasing the dose as needed.

In this study, the pharmacokinetics of a newly introduced dosing regimen for posaconazole oral suspension is investigated, based on body surface area (BSA), used prophylactically in immunocompromised children under the age of 13.

Pediatric patients, admitted to the hospital to receive chemotherapy or hematopoietic stem cell transplantation are treated prophylactically with posaconazole 120mg/m² tid.

At steady state (after at least 7 days of posaconazole treatment), 9 plasma samples are collected in these patients to calculate the area under the curve and other relevant PK parameters as maximum and minimal plasma concentrations, volume of distribution, halflife and clearance rate.

Finally, these results will be compared to adult data in literature to evaluate whether 120mg/m² tid an adequate dosing regimen in children.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Hematological Malignancy
Intervention  ICMJE
  • Drug: Posaconazole prophylaxis 120 mg/m² tid
    Patients are receiving posaconazole to prevent invasive fungal infections in a dose of 120 mg/m² tid
  • Procedure: Blood sampling
    During steady state treatment with posaconazole (at least 7 days), 9 blood samples are taken via a central venous catheter to evaluate the pharmacokinetics of posaconazole.
Study Arms  ICMJE Experimental: Posaconazole 120mg/m² tid

Pediatric patients admitted to receive chemotherapy or hematopoietic stem cell transplantation for the treatment of a hematological malignancy are receiving Posaconazole prophylaxis 120 mg/m² tid.

At steady state, blood sampling will be performed: 9 blood samples will be taken during 1 dosing interval to evaluate the pharmacokinetics of posaconazole.

Interventions:
  • Drug: Posaconazole prophylaxis 120 mg/m² tid
  • Procedure: Blood sampling
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2015)
14
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 2-13 years of age
  • hematological malignancy
  • need for antifungal prophylaxis because of neutropenia caused by chemotherapy and/or hematopoietic stem cell transplantation.

Exclusion Criteria:

  • <2 years of age
  • > 13 years of age
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 13 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Romania
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02372357
Other Study ID Numbers  ICMJE 2841/20 Feb 2012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ap.r Kim Vanstraelen, Universitaire Ziekenhuizen Leuven
Study Sponsor  ICMJE Universitaire Ziekenhuizen Leuven
Collaborators  ICMJE Institutul Clinic Fundeni
Investigators  ICMJE
Principal Investigator: Anca Colita, MD Institutul Clinic Fundeni, Bucarest, Romania
Principal Investigator: Kim Vanstraelen, PharmD Catholic University Leuven, Leuven, Belgium
PRS Account Universitaire Ziekenhuizen Leuven
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP