Cytomegalovirus InfectionsNCT03698435
(Val)Ganciclovir TDM in Transplant Recipients
An observational study of Cytomegalovirus Infections, run by University Medical Center Groningen at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- Ganciclovir and Valganciclovir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 May 2018to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- There are no exclusion criteria.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
UMCG
Groningen
JWC Alffenaar, PhD
About this study
Official title: (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.
Read the 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.
- Conditions
- Cytomegalovirus Infections
- Being tested
- Ganciclovir, Valganciclovir
- Keywords
- ganciclovir, valganciclovir, therapeutic drug monitoring, pharmacokinetics
- Medical subject headings
- Cytomegalovirus Infections, Multiple Acyl Coenzyme A Dehydrogenase Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanciclovirDrug
Also called Cymevene
Intravenous ganciclovir + TDM
ValganciclovirDrug
Also called Valcyte
Oral valganciclovir + TDM
| Study group | Role | What they receive |
|---|---|---|
| Prophylaxis | Patients who receive (val)ganciclovir for prophylaxis of cytomegalovirus Receives: Drug: Ganciclovir; Drug: Valganciclovir | |
| Treatment | Patients who receive (val)ganciclovir for treatment of cytomegalovirus Receives: Drug: Ganciclovir; Drug: Valganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months after transplantation
Secondary outcomes (8)
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
Measured: 12 months after transplantation
Therapeutic window
How many levels are in and out of the therapeutic window (how many low and high levels)?
Measured: 12 months after transplantation
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).
Measured: 12 months after transplantation
(Val)ganciclovir for treatment outcomes (1)
The proportion of patients from CMV treatment group who are under-dosed
Measured: 12 months after transplantation
(Val)ganciclovir for treatment outcomes (2)
The proportion of patients from CMV treatment group who develop resistance to ganciclovir
Measured: 12 months after transplantation
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.
Measured: 12 months after transplantation
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.
Measured: 12 months after transplantation
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.
Measured: 12 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2018
- Study start25 May 2018
- Primary completion30 Nov 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jan-Willem C Alffenaar, University Medical Center Groningen
- Investigators
- Jan-Willem Alffenaar, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03698435
- Sponsor's protocol ID
- 201800021
- Status last verified
- Oct 2019
- First submitted
- 7 Feb 2018
- Last updated
- 10 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients
- ClinicalTrials.gov ID
- NCT03698435
- Acronym / sponsor ID
- 201800021
- Conditions
- Cytomegalovirus Infections
- Keywords
- ganciclovir, valganciclovir, therapeutic drug monitoring, pharmacokinetics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 25 May 2018 (actual)
- Primary completion
- 30 Nov 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 9 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prophylaxis | – | Drug: Ganciclovir, Drug: ValganciclovirPatients who receive (val)ganciclovir for prophylaxis of cytomegalovirus |
| Treatment | – | Drug: Ganciclovir, Drug: ValganciclovirPatients who receive (val)ganciclovir for treatment of cytomegalovirus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- There are no exclusion criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GanciclovirAlso: CymeveneIntravenous ganciclovir + TDM | Drug | Prophylaxis, Treatment |
| ValganciclovirAlso: ValcyteOral valganciclovir + TDM | Drug | Prophylaxis, Treatment |
Primary outcome
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.
8 secondary outcomes
Breakthrough CMV infection during CMV prophylaxis with valganciclovir
Time frame: 12 months after transplantation
Therapeutic window
Time frame: 12 months after transplantation
Successful treatment while receiving (val)ganciclovir determined by two consequtive negative viral loads
Time frame: 12 months after transplantation
(Val)ganciclovir for treatment outcomes (1)
Time frame: 12 months after transplantation
(Val)ganciclovir for treatment outcomes (2)
Time frame: 12 months after transplantation
Factors that can influence trough concentrations of (val)ganciclovir (1)
Time frame: 12 months after transplantation
Factors that can influence trough concentrations of (val)ganciclovir (2)
Time frame: 12 months after transplantation
Factors that can influence trough concentrations of (val)ganciclovir (3)
Time frame: 12 months after transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
Related trials for Cytomegalovirus Infections
RecruitingObservational study
A Study of LIVTENCITY (Maribavir) in Adults With Cytomegalovirus (CMV) Infection After Transplantation in South Korea
Cytomegalovirus (CMV)
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingPhase 2
CMV CTLs in Neonates With CMV Infection
Congenital Cytomegaloviral (CMV) Disease
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan-Willem Alffenaar, PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infections, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anne-Grete Märtson, MSc (+37253325121, a.martson@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 12 months after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.