Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients

Study Overview
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Brief Summary
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Herpesvirus infections may be severe in immunocompromised patients, with a high risk of complications and mortality. Recipients of hematopoietic stem cell transplant (HSCT) or patients receiving high-intensity chemotherapy for hematological malignancies are the most vulnerable individuals. Although the worldwide prevalence of herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV), antiviral prophylaxis in seropositive HSCT recipients has significantly reduced the rate of infection. Acyclovir (ACV) is the first-choice drug for the prophylaxis or the therapy of that kind of infection. Since the beginning, ACV has demonstrated to be characterized by a large interpatient variability, especially in children. Therefore, therapeutic drug monitoring and pharmacokinetic studies may help in optimizing drug in children with malignancies.

Detailed Description
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Herpesvirus infections may lead to severe disease with a high risk of complications and mortality in hematopoietic stem cell transplant (HSCT) recipients, or in patients receiving high-intensity chemotherapy for hematological malignancies. That risk is mainly associated with the worldwide prevalence of herpes simplex virus 1 (HSV-1) that increases consistently with age. In particular, the majority of adult leukemia patients are HSV seropositive, while allogeneic HSCT recipients had post-transplant HSV reactivation. It is worth noting that in the first post-transplant year, symptomatic varicella-zoster virus (VZV) reactivation has a rate of 13% - 55% in adult recipients. Similar percentages of children receiving HSCT had VZV reactivation, being also possible a disseminated infection in 10% of children. However, thanks to antiviral prophylaxis in seropositive HSCT recipients, the rate of infection has significantly dropped. Among the drugs most used for treatment and prophylaxis of HSV/VZV infections among children who are HSCT recipients or undergo a high-intensity chemotherapy, acyclovir represents the drug of choice. Although its role in preventing and treating herpes virus infections, the pharmacokinetics of acyclovir is highly variable, especially in patients in intensive care units, in those who have organ dysfunction, or in children. In particular, information about the optimal use of acyclovir in children with malignancies is limited.

Official Title
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Pharmacokinetics of Intravenous Acyclovir in Children Undergoing Hematopoietic Stem Cell Transplantation or High-intensity Antineoplastic Chemotherapy

Conditions
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Herpesviridae Infections, Herpes Simplex 1, Varicella Zoster Virus Infection, Transplantation Infection, Oncology

Intervention / Treatment
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* Other: Pharmacokinetic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Hematological malignancies HSCT recipients who require ACV prophylaxis or treatment for HSV-VZV infection or Children undergoing high-intensity antineoplastic chemotherapy who need ACV treatment. Intravenous or oral ACV dosing Active/available a therapeutic drug monitoring (TDM) protocol for ACV Informed consent signed by patient's parents Exclusion Criteria: lack of signed informed consent lack of TDM for ACV unavailable patient's demographic characteristics

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intravenous Aciclovir<br>Patients receiving intravenous aciclovir for prophylaxis or treatment of herpes virus infections | Other: Pharmacokinetic analysis<br>* Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring<br>|
| Oral Aciclovir<br>Patients receiving oral aciclovir/valaciclovir for prophylaxis or treatment of herpes virus infections | Other: Pharmacokinetic analysis<br>* Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who achieve an acyclovir minimum plasma concentration of 0.5 mg/L at steady state | Percentage of patients who achieve an acyclovir minimum plasma concentration at steady state ≥0.5 mg/L, considered as an effective plasma concentration | Six months since the beginning of acyclovir administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic stem cell transplantation, Herpes virus infections, Aciclovir, Children, Pharmacokinetics