- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03698435
(Val)Ganciclovir TDM in Transplant Recipients
(Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Anne-Grete Märtson, MSc
- Phone Number: +37253325121
- Email: a.martson@umcg.nl
Study Contact Backup
- Name: Marjolein Knoester, MD
- Phone Number: +31503613480
- Email: m.knoester@umcg.nl
Study Locations
-
-
-
Groningen, Netherlands
- Recruiting
- UMCG
-
Contact:
- JWC Alffenaar, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
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
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:
Oral valganciclovir + TDM
Other Names:
|
Treatment
Patients who receive (val)ganciclovir for treatment of cytomegalovirus
|
Intravenous ganciclovir + TDM
Other Names:
Oral valganciclovir + TDM
Other Names:
|
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
Investigators
- Principal Investigator: Jan-Willem Alffenaar, PhD, University Medical Center Groningen
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201800021
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
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