Contact information
Type
Scientific
Primary contact
Miss Nancy Perrottet
ORCID ID
Contact details
Division de Pharmacologie et Toxicologie Cliniques
Hôpital de Beaumont - 06.605
Lausanne
1011
Switzerland
Nancy.Perrottet@chuv.ch
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
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
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).
Study design
Prospective observational trial with historical controls
Primary study design
Observational
Secondary study design
Case-control study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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 names
Valganciclovir
Primary outcome measure
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
Secondary outcome measures
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
Overall trial start date
15/11/2005
Overall trial end date
31/12/2007
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
100
Participant exclusion criteria
1. Failure to give written informed consent
2. Known intolerance to ganciclovir or valganciclovir
Recruitment start date
15/11/2005
Recruitment end date
31/12/2007
Locations
Countries of recruitment
Switzerland
Trial participating centre
Division de Pharmacologie et Toxicologie Cliniques
Lausanne
1011
Switzerland
Sponsor information
Organisation
University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland)
Sponsor details
Rue du Bugnon 46
Lausanne
1011
Switzerland
+ 41 (0)21 314 11 11
info@chuv.ch
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Roche (Switzerland) - unrestricted grant
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list