Clinical trial NCT03698435: (Val)Ganciclovir TDM in Transplant Recipients
Official title: (Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cytomegalovirus Infections
Keywords: ganciclovir
valganciclovir
therapeutic drug monitoring
pharmacokinetics
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2018-10-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing solid organ or stem cell transplantation are at risk of developing cytomegalovirus (CMV) infection or reactivation. Valganciclovir (oral pro-drug of ganciclovir) prophylaxis is used to postpone CMV infection or reactivation to a later point in the post-transplantation.

Brief summary: The aim of this study is to gain more insight into therapeutic drug monitoring and thus the pharmacodynamics and pharmacokinetics of ganciclovir, in the context of prophylaxis and treatment of CMV infections, in order to provide the patient with an adequate dose.

Detailed description: Patients undergoing solid organ or stem cell transplantation are at risk of developing cytomegalovirus (CMV) infection or reactivation. The risk of CMV infection / reactivation and its severity depends on the CMV serostatus of donor and recipient. Valganciclovir (oral pro-drug of ganciclovir) prophylaxis is used to postpone CMV infection or reactivation to a later point in the post-transplantation.

CMV infection/reactivation does not always lead to clinical disease. Valganciclovir (oral) can be used when CMV DNA is detected in the blood, but patient has no or few complaints. However, in case of severe symptoms such as colitis, nephritis, hepatitis, pneumonitis, uveitis or encephalitis (active CMV disease) then ganciclovir is indicated intravenously. In clinical recovery treatment is often completed with valganciclovir.

It is important that the ganciclovir level is adequate, because too high level can lead to side effects such as cytopenia and a too low level can lead to treatment failure and resistance development. There are different dosing schedules mentioned in different sources. These schemes are based on dated literature.

The aim of (val)ganciclovir therapeutic drug monitoring (TDM) is to gain more insight into the pharmacodynamics and pharmacokinetics of ganciclovir, in the context of prophylaxis and treatment of CMV infections, in order to provide the patient with an adequate dose.

Eligibility criteria: Inclusion Criteria:

* Must receive ganciclovir intravenously or valganciclovir orally as routine care
* Must have received a solid organ or stem cell transplant
* Must be be 18 years or older

Exclusion Criteria:

There are no exclusion criteria.

Primary outcomes:
measure: Failure of CMV treatment (with valganciclovir and ganciclovir) using viral load measurements and determining mutations in CMV kinase gene UL97 and DNA polymerase gene UL54
timeFrame: 12 months after transplantation
Secondary outcomes:
measure: Breakthrough CMV infection during CMV prophylaxis with valganciclovir
timeFrame: 12 months after transplantation
measure: Therapeutic window
timeFrame: 12 months after transplantation
measure: Successful treatment while receiving (val)ganciclovir determined by two consequtive negative viral loads
timeFrame: 12 months after transplantation
measure: (Val)ganciclovir for treatment outcomes (1)
timeFrame: 12 months after transplantation
measure: (Val)ganciclovir for treatment outcomes (2)
timeFrame: 12 months after transplantation
measure: Factors that can influence trough concentrations of (val)ganciclovir (1)
timeFrame: 12 months after transplantation
measure: Factors that can influence trough concentrations of (val)ganciclovir (2)
timeFrame: 12 months after transplantation
measure: Factors that can influence trough concentrations of (val)ganciclovir (3)
timeFrame: 12 months after transplantation
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: UMCG
Study officials:
affiliation: University Medical Center Groningen
name: Jan-Willem Alffenaar, PhD
role: PRINCIPAL_INVESTIGATOR
References: