A pharmacokinetic and pharmacodynamic study of valganciclovir in solid organ transplant patients

ISRCTN	ISRCTN06404801
DOI	https://doi.org/10.1186/ISRCTN06404801
Protocol serial number	N/A
Sponsor	University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland)
Funders	University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland), Roche (Switzerland) - unrestricted grant

Submission date: 11/12/2006
Registration date: 14/02/2007
Last edited: 19/07/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Miss Nancy Perrottet
Scientific

Division de Pharmacologie et Toxicologie Cliniques
Hôpital de Beaumont - 06.605
Lausanne
1011
Switzerland

Email	Nancy.Perrottet@chuv.ch

Study information

Primary study design	Observational
Study design	Prospective observational trial with historical controls
Secondary study design	Case-control study
Scientific title	A pharmacokinetic and pharmacodynamic study of valganciclovir in solid organ transplant patients
Study objectives	Valganciclovir is a prodrug of ganciclovir with improved oral bioavailability, potentially useful for the treatment of Cytomegalovirus (CMV) infection in organ transplant recipients and for the prophylaxis of CMV infection in liver and lung transplant patients, two indications currently not validated. Our hypothesis is that valganciclovir produces drug levels and virological responses similar to those obtained with intravenous ganciclovir. This would provide indirect evidence for the use of oral valganciclovir instead of intravenous ganciclovir within the settings mentioned above.
Ethics approval(s)	Approval received by the local ethics committee (Commission déthique de la recherche clinique, Faculté de Médecine et Biologie, Université de Lausanne) on the 20th September 2005 (ref: 94/05).
Health condition(s) or problem(s) studied	Cytomegalovirus (CMV) infection
Intervention	Patients will receive valganciclovir (900 mg once daily [QD], adjusted to their renal function according to the information provided by the manufacturer), over three months, for primary prophylaxis. During such period, blood samples will be collected monthly to determine ganciclovir plasma levels (immediately before and three hours after oral administration) and CMV blood viral loads will be measured by real time quantitative Polymerase Chain Reaction (PCR). Upon the initial prophylaxis termination, and over the following three months, universal blood monitoring for CMV infection will continue on a fortnightly basis. In case of detection of high viremia level (more than 10,000 - 100,000 copies of CMV Deoxyribonucleic Acid [DNA]/million leukocytes) and/or symptomatic CMV disease, patients will receive therapeutic dosages of valganciclovir (900 mg twice daily [bid], adjusted to renal function) until they achieve a clinical response or their viral load drops. Throughout such treatment phase, ganciclovir plasma level and CMV viral load assays will be performed weekly. Treated subjects will then receive secondary prophylaxis (half the therapeutic dose of valganciclovir, 900 mg QD, adjusted to renal function) for one month, with fortnightly ganciclovir plasma levels and CMV viral load assays. In selected patients, treating physicians may opt at their discretion for intravenous ganciclovir rather than oral valganciclovir, based on their clinical judgement. Any such patients will have plasma levels and CMV viral load tested weekly.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Valganciclovir
Primary outcome measure(s)	1. To determine whether the average ganciclovir blood levels following the oral administration of valganciclovir are comparable to the known therapeutic range associated with the use of intravenous ganciclovir 2. To assess the variability of ganciclovir blood levels attained with oral valganciclovir, to evaluate its potential repercussions on therapeutic response, and to identify influential factors which modulate valganciclovir absorption and disposition
Key secondary outcome measure(s)	1. To evaluate the relationship between ganciclovir blood levels and anti-CMV efficacy using a pharmacokinetic-pharmacodynamic model incorporating the relevant pharmacokinetic, virological and clinical response parameters 2. To determine the impact of specific clinical conditions (malabsorption, cystic fibrosis, kidney failure), concomitant medications (drugs inhibiting organic anion transport) and possibly genetic traits (drug transporters polymorphisms) on ganciclovir and valganciclovir pharmacokinetics and dose requirements 3. To further assess the safety and tolerability of oral valganciclovir
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	100
Key inclusion criteria	1. Solid organ transplant recipient 2. More than or equal to 18 years old 3. At risk for CMV disease (D+/R-, D+/R+ or D-/R+) 4. Written informed consent
Key exclusion criteria	1. Failure to give written informed consent 2. Known intolerance to ganciclovir or valganciclovir
Date of first enrolment	15/11/2005
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

Switzerland

Study participating centre

Division de Pharmacologie et Toxicologie Cliniques

Lausanne
1011
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Thesis results		26/05/2008	19/07/2021	No	No

Editorial Notes

19/07/2021: Link to thesis added.