Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients

NCT ID: NCT05198570

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-09-15
• Study Completion Date: 2026-03-31

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.

Conditions

Herpesviridae Infections; Herpes Simplex 1; Varicella Zoster Virus Infection; Transplantation Infection; Oncology

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

Intravenous Aciclovir

Patients receiving intravenous aciclovir for prophylaxis or treatment of herpes virus infections

Pharmacokinetic analysis

Intervention Type: OTHER

Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring

Oral Aciclovir

Patients receiving oral aciclovir/valaciclovir for prophylaxis or treatment of herpes virus infections

Pharmacokinetic analysis

Intervention Type: OTHER

Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring

Interventions

Pharmacokinetic analysis

Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring

Intervention Type: OTHER

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Burlo Garofolo

OTHER

Sponsor Role: collaborator

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Antonello Di Paolo, M.D., Ph.D.

Associate Professor of Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Natalia Maximova, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Burlo Garofolo

Locations

IRCCS Burlo Garofolo, Bone Marrow Transplant Unit, Institute for Maternal and Child Health

Trieste, TS, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Natalia Maximova, MD

Role: CONTACT

natalia-maximova@burlo.trieste.it

040 378 5111 ext. 565

Facility Contacts

Natalia Maximova, MD

Role: primary

natalia.maximova@burlo.trieste.it

References

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.

Reference Type: RESULT

PMID: 35496277 (View on PubMed)

Other Identifiers

RC_10/20

Identifier Type: -

Identifier Source: org_study_id