(Val)Ganciclovir TDM in Transplant Recipients

Cytomegalovirus Infections Clinical Trial

Official title:

(Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03698435
• Other study ID #: 201800021
• Status: Recruiting
• Start date: May 25, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: October 2019
• Source: University Medical Center Groningen
• Contact: Anne-Grete Märtson, MSc
• Phone: +37253325121
• Email: a.martson[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2019
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cytomegalovirus Infections

Intervention

Drug:
• Ganciclovir
Intravenous ganciclovir + TDM
• Valganciclovir
Oral valganciclovir + TDM

Locations

Country	Name	City	State
Netherlands	UMCG	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	12 months after transplantation
Secondary	Breakthrough CMV infection during CMV prophylaxis with valganciclovir	Breakthrough CMV infection during prophylaxis with valganciclovir, time (days) to development of breakthrough CMV infection during prophylaxis	12 months after transplantation
Secondary	Therapeutic window	How many levels are in and out of the therapeutic window (how many low and high levels)?	12 months after transplantation
Secondary	Successful treatment while receiving (val)ganciclovir determined by two consequtive negative viral loads	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).	12 months after transplantation
Secondary	(Val)ganciclovir for treatment outcomes (1)	The proportion of patients from CMV treatment group who are under-dosed	12 months after transplantation
Secondary	(Val)ganciclovir for treatment outcomes (2)	The proportion of patients from CMV treatment group who develop resistance to ganciclovir	12 months after transplantation
Secondary	Factors that can influence trough concentrations of (val)ganciclovir (1)	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.	12 months after transplantation
Secondary	Factors that can influence trough concentrations of (val)ganciclovir (2)	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.	12 months after transplantation
Secondary	Factors that can influence trough concentrations of (val)ganciclovir (3)	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.	12 months after transplantation