(Val)Ganciclovir TDM in Transplant Recipients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Prophylaxis Patients who receive (val)ganciclovir for prophylaxis of cytomegalovirus |
Drug: Ganciclovir
Intravenous ganciclovir + TDM
Other Names:
Drug: Valganciclovir
Oral valganciclovir + TDM
Other Names:
|
| Treatment Patients who receive (val)ganciclovir for treatment of cytomegalovirus |
Drug: Ganciclovir
Intravenous ganciclovir + TDM
Other Names:
Drug: Valganciclovir
Oral valganciclovir + TDM
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 [12 months after transplantation]
How many days to the development of failure of treatment? Failure of treatment is defined by increased viral load (measured in serum, whole blood, plasma in copies per mL and/or viral resistance (change of ganciclovir treatment to foscarnet treatment as a consequence, resistance is determined by resistance testing determining CMV kinase gene UL97 and DNA polymerase gene UL54 for mutations) or death due to CMV.
Secondary Outcome Measures
- Breakthrough CMV infection during CMV prophylaxis with valganciclovir [12 months after transplantation]
Breakthrough CMV infection during prophylaxis with valganciclovir, time (days) to development of breakthrough CMV infection during prophylaxis
- Therapeutic window [12 months after transplantation]
How many levels are in and out of the therapeutic window (how many low and high levels)?
- Successful treatment while receiving (val)ganciclovir determined by two consequtive negative viral loads [12 months after transplantation]
The proportion of patients from CMV treatment group who have a successful CMV treatment, successful CMV treatment is defined by viral load <100 copies/mL (measured twice in a row).
- (Val)ganciclovir for treatment outcomes (1) [12 months after transplantation]
The proportion of patients from CMV treatment group who are under-dosed
- (Val)ganciclovir for treatment outcomes (2) [12 months after transplantation]
The proportion of patients from CMV treatment group who develop resistance to ganciclovir
- Factors that can influence trough concentrations of (val)ganciclovir (1) [12 months after transplantation]
Does the type of transplanted organ (liver, lungs, kidney, heart, stem cell transplant) cause high or low (val)ganciclovir trough concentrations (mg/L)? Defined therapeutic window for prophylaxis is 1-2 mg/L and for therapy is 2-4 mg/L. Number of levels which are out of the therapeutic window for different transplants.
- Factors that can influence trough concentrations of (val)ganciclovir (2) [12 months after transplantation]
Does the underlying disease for transplantation cause high or low (val)ganciclovir trough concentrations (mg/L)? Defined therapeutic window for prophylaxis is 1-2 mg/L and for therapy is 2-4 mg/L. Number of levels which are out of the therapeutic window for different underlying diseases.
- Factors that can influence trough concentrations of (val)ganciclovir (3) [12 months after transplantation]
Does dose reduction for renal failure cause increase or decrease in (val)ganciclovir trough concentrations (mg/L)? Number of levels which are out of the therapeutic window after dose reduction.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UMCG | Groningen | Netherlands |
Sponsors and Collaborators
- University Medical Center Groningen
Investigators
- Principal Investigator: Jan-Willem Alffenaar, PhD, University Medical Center Groningen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 201800021