Clinical trial NCT05198570: Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients
Official title: Pharmacokinetics of Intravenous Acyclovir in Children Undergoing Hematopoietic Stem Cell Transplantation or High-intensity Antineoplastic Chemotherapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Herpesviridae Infections
Herpes Simplex 1
Varicella Zoster Virus Infection
Transplantation Infection
Oncology
Keywords: Hematopoietic stem cell transplantation
Herpes virus infections
Aciclovir
Children
Pharmacokinetics
Lead sponsor: University of Pisa
Sponsor class: OTHER
Collaborators: name: IRCCS Burlo Garofolo
First posted: 2022-01-20
Enrollment: 200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 0-18 years, affected by hematological malignancies, undergoing ACV prophylaxis or treatment for HSV-VZV infection routinely during allogeneic HSCT or ACV treatment during high-intensity chemotherapy, for who a therapeutic drug monitoring (TDM) protocol is available. Patients receive ACV as a standard 1-h intravenous infusion or through the oral administration of valaciclovir

Brief summary: * 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients who achieve an acyclovir minimum plasma concentration of 0.5 mg/L at steady state
timeFrame: Six months since the beginning of acyclovir administration
Secondary outcomes:
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: IRCCS Burlo Garofolo, Bone Marrow Transplant Unit, Institute for Maternal and Child Health
state: TS
Study officials:
affiliation: IRCCS Burlo Garofolo
name: Natalia Maximova, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maximova N, Nistico D, Luci G, Simeone R, Piscianz E, Segat L, Barbi E, Di Paolo A. Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients. Front Pharmacol. 2022 Apr 14;13:865871. doi: 10.3389/fphar.2022.865871. eCollection 2022.