Pharmacokinetics of Intravenous Acyclovir in Oncologic Paediatric Patients
Study Details
Study Description
Brief Summary
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Herpesvirus infections may be severe in immunocompromised patients, with a high risk of complications and mortality.
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Recipients of hematopoietic stem cell transplant (HSCT) or patients receiving high-intensity chemotherapy for hematological malignancies are the most vulnerable individuals.
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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.
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Acyclovir (ACV) is the first-choice drug for the prophylaxis or the therapy of that kind of infection.
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Since the beginning, ACV has demonstrated to be characterized by a large interpatient variability, especially in children.
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Therefore, therapeutic drug monitoring and pharmacokinetic studies may help in optimizing drug in children with malignancies.
Condition or Disease | Intervention/Treatment | Phase |
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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
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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
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Outcome Measures
Primary Outcome Measures
- 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
Inclusion Criteria:
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Patients with Hematological malignancies
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HSCT recipients who require ACV prophylaxis or treatment for HSV-VZV infection or
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Children undergoing high-intensity antineoplastic chemotherapy who need ACV treatment.
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Intravenous or oral ACV dosing
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Active/available a therapeutic drug monitoring (TDM) protocol for ACV
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Informed consent signed by patient's parents
Exclusion Criteria:
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lack of signed informed consent
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lack of TDM for ACV
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unavailable patient's demographic characteristics
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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
- Beyar-Katz O, Bitterman R, Zuckerman T, Ofran Y, Yahav D, Paul M. Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis. Clin Microbiol Infect. 2020 Feb;26(2):189-198. doi: 10.1016/j.cmi.2019.09.003. Epub 2019 Sep 16.
- Buus-Gehrig C, Bochennek K, Hennies MT, Klingebiel T, Groll AH, Lehrnbecher T. Systemic viral infection in children receiving chemotherapy for acute leukemia. Pediatr Blood Cancer. 2020 Dec;67(12):e28673. doi: 10.1002/pbc.28673. Epub 2020 Sep 12. Review.
- Czyzewski K, Dziedzic M, Salamonowicz M, Fraczkiewicz J, Zajac-Spychala O, Zaucha-Prazmo A, Gozdzik J, Galazka P, Bartoszewicz N, Demidowicz E, Styczynski J. Epidemiology, Outcome and Risk Factors Analysis of Viral Infections in Children and Adolescents Undergoing Hematopoietic Cell Transplantation: Antiviral Drugs Do Not Prevent Epstein-Barr Virus Reactivation. Infect Drug Resist. 2019 Dec 17;12:3893-3902. doi: 10.2147/IDR.S224291. eCollection 2019.
- Dadwal SS. Herpes Virus Infections Other than Cytomegalovirus in the Recipients of Hematopoietic Stem Cell Transplantation. Infect Dis Clin North Am. 2019 Jun;33(2):467-484. doi: 10.1016/j.idc.2019.02.012. Review.
- Fisher BT, Alexander S, Dvorak CC, Zaoutis TE, Zerr DM, Sung L. Epidemiology and potential preventative measures for viral infections in children with malignancy and those undergoing hematopoietic cell transplantation. Pediatr Blood Cancer. 2012 Jul 15;59(1):11-5. doi: 10.1002/pbc.23417. Epub 2011 Nov 18. Review.
- Styczynski J, Reusser P, Einsele H, de la Camara R, Cordonnier C, Ward KN, Ljungman P, Engelhard D; Second European Conference on Infections in Leukemia. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009 May;43(10):757-70. doi: 10.1038/bmt.2008.386. Epub 2008 Dec 1.
- Zeng L, Nath CE, Blair EY, Shaw PJ, Stephen K, Earl JW, Coakley JC, McLachlan AJ. Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir. Antimicrob Agents Chemother. 2009 Jul;53(7):2918-27. doi: 10.1128/AAC.01138-08. Epub 2009 May 4.
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