Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients

Sponsor
University of Pisa (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT05198570
Collaborator
IRCCS Burlo Garofolo (Other)
200
1
18.5
10.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Pharmacokinetic analysis

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 Design

Study Type:
Observational
Anticipated Enrollment :
200 participants
Observational Model:
Case-Only
Time Perspective:
Retrospective
Official Title:
Pharmacokinetics of Intravenous Acyclovir in Children Undergoing Hematopoietic Stem Cell Transplantation or High-intensity Antineoplastic Chemotherapy
Actual Study Start Date :
Sep 15, 2021
Anticipated Primary Completion Date :
Sep 15, 2022
Anticipated Study Completion Date :
Mar 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Intravenous Aciclovir

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

Other: Pharmacokinetic analysis
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

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

Outcome Measures

Primary Outcome Measures

  1. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 IRCCS Burlo Garofolo, Bone Marrow Transplant Unit, Institute for Maternal and Child Health Trieste TS Italy 34137

Sponsors and Collaborators

  • University of Pisa
  • IRCCS Burlo Garofolo

Investigators

  • Principal Investigator: Natalia Maximova, MD, IRCCS Burlo Garofolo

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Antonello Di Paolo, M.D., Ph.D., Associate Professor of Pharmacology, University of Pisa
ClinicalTrials.gov Identifier:
NCT05198570
Other Study ID Numbers:
  • RC_10/20
First Posted:
Jan 20, 2022
Last Update Posted:
Jan 20, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Antonello Di Paolo, M.D., Ph.D., Associate Professor of Pharmacology, University of Pisa
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 20, 2022