Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients

Recruiting

• Conditions: Herpes Simplex 1; Varicella Zoster Virus Infection; Transplantation Infection; Herpesviridae Infections; Oncology
• Interventions: Other: Pharmacokinetic analysis

• Registration Number: NCT05198570
• Lead Sponsor: University of Pisa

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.

Study Timeline

• Study Start: 2021-09-15
• Study First Submitted: 2022-01-04
• Study First Submitted QC: 2022-01-19
• Study First Posted: 2022-01-20
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-05
• Last Update Posted: 2023-10-10
• Primary Completion: 2023-12-31
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intravenous Aciclovir	Pharmacokinetic analysis	Patients receiving intravenous aciclovir for prophylaxis or treatment of herpes virus infections
Oral Aciclovir	Pharmacokinetic analysis	Patients receiving oral aciclovir/valaciclovir for prophylaxis or treatment of herpes virus infections

Primary Outcome Measures

Name	Time	Method
Percentage of patients who achieve an acyclovir minimum plasma concentration of 0.5 mg/L at steady state	Six months since the beginning of acyclovir administration	Percentage of patients who achieve an acyclovir minimum plasma concentration at steady state ≥0.5 mg/L, considered as an effective plasma concentration

Trial Locations

Locations (1)

IRCCS Burlo Garofolo, Bone Marrow Transplant Unit, Institute for Maternal and Child Health; 🇮🇹 Trieste, TS, Italy