(Val)Ganciclovir TDM in Transplant Recipients

October 8, 2019 updated by: Jan-Willem C Alffenaar, University Medical Center Groningen

(Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients

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.

Study Overview

Status

Unknown

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 Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Groningen, Netherlands
        • Recruiting
        • UMCG
        • Contact:
          • JWC Alffenaar, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Prophylaxis
Patients who receive (val)ganciclovir for prophylaxis of cytomegalovirus
Intravenous ganciclovir + TDM
Other Names:
  • Cymevene
Oral valganciclovir + TDM
Other Names:
  • Valcyte
Treatment
Patients who receive (val)ganciclovir for treatment of cytomegalovirus
Intravenous ganciclovir + TDM
Other Names:
  • Cymevene
Oral valganciclovir + TDM
Other Names:
  • Valcyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
12 months after transplantation

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jan-Willem Alffenaar, PhD, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2018

Primary Completion (Anticipated)

November 30, 2019

Study Completion (Anticipated)

December 31, 2019

Study Registration Dates

First Submitted

February 7, 2018

First Submitted That Met QC Criteria

October 3, 2018

First Posted (Actual)

October 9, 2018

Study Record Updates

Last Update Posted (Actual)

October 10, 2019

Last Update Submitted That Met QC Criteria

October 8, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cytomegalovirus Infections

Clinical Trials on Ganciclovir

3
Subscribe