Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients

Oncology Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05198570
• Other study ID #: RC_10/20
• Status: Recruiting
• Start date: September 15, 2021
• Est. completion date: March 31, 2024

Study information

• Verified date: October 2023
• Source: University of Pisa
• Contact: Natalia Maximova, MD
• Phone: 040 378 5111
• Email: natalia-maximova[@]burlo.trieste.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Herpes Simplex
• Herpes Simplex 1
• Herpes Zoster
• Herpesviridae Infections
• Infections
• Oncology
• Transplantation Infection
• Varicella Zoster Virus Infection
• Virus Diseases

Intervention

Other:
• Pharmacokinetic analysis
Population pharmacokinetic analysis of plasma concentrations of aciclovir obtained during routine therapeutic drug monitoring

Locations

Country	Name	City	State
Italy	IRCCS Burlo Garofolo, Bone Marrow Transplant Unit, Institute for Maternal and Child Health	Trieste	TS

Sponsors (2)

Lead Sponsor	Collaborator
University of Pisa	IRCCS Burlo Garofolo

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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