A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area
Condition: Hematological Malignancy
MeSH terms: Hematologic Neoplasms
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Posaconazole prophylaxis 120 mg/m² tid; Blood sampling
Intervention type(s): Drug; Procedure
Intervention description(s): Patients are receiving posaconazole to prevent invasive fungal infections in a dose of 120 mg/m² tid; 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.
Intervention MeSH terms: Posaconazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: chemotherapy; stem cell transplantation