A pharmacokinetic and pharmacodynamic study of valganciclovir in solid organ transplant patients
| ISRCTN | ISRCTN06404801 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN06404801 |
| Secondary identifying numbers | N/A |
- 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
Scientific
Division de Pharmacologie et Toxicologie Cliniques
Hôpital de Beaumont - 06.605
Lausanne
1011
Switzerland
| Nancy.Perrottet@chuv.ch |
Study information
| Study design | Prospective observational trial with historical controls |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 15/11/2005 |
| Completion date | 31/12/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Not Specified |
| Target number of participants | 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
1011
Switzerland
Sponsor information
University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland)
Hospital/treatment centre
Hospital/treatment centre
Rue du Bugnon 46
Lausanne
1011
Switzerland
| Phone | + 41 (0)21 314 11 11 |
|---|---|
| info@chuv.ch | |
| Website | http://www.chuv.ch/ |
Funders
Funder type
Hospital/treatment centre
University Hospital Complex of Vaud (Centre Hospitalier Universitaire Vaudois [CHUV]) (Switzerland)
No information available
Roche (Switzerland) - unrestricted grant
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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.
