Clinical trial NCT01446445: Individualization of Ganciclovir and Valganciclovir Doses Using Bayesian Prediction in Renal Transplant Patients.
Official title: Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infection in Solid Organ Transplant Recipients
Keywords: Cytomegalovirus
renal transplant
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Ministerio de Sanidad, Servicios Sociales e Igualdad
First posted: 2011-10-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the present study is to optimize intravenous ganciclovir(GCV) and oral valganciclovir (VGCV)doses, advised by the drug exposure, indicated by the area under the concentration time curve (AUC), in renal transplant patients receiving oral VGCV or intravenous GCV for CMV prophylaxis or treatment. The initial doses will be calculated according to population pharmacokinetic model. Subsequent doses will be adjusted according to plasma GCV concentrations, using the Bayesian approach. This method of dose adjustments could lead to increase the percentage of patients achieving a therapeutic exposure.

Detailed description: The area under the concentration time curve of serum concentrations of GCV is an indicator of systemic exposure to the drug and is related to the effectiveness and safety. According to the population model developed by our group, less than 16% of patients treated achieve the therapeutic goal of AUC (40 to 50 mcg • h / L) after drug dosing according to summary of product characteristics (SPC). Especially, patients with impaired renal function values (creatinine clearance (CrC)l \<30 ml / min) or high (CrCl\> 70 ml / min) would be overdosed and underdosed, respectively, with the risk of more adverse effects or therapeutic failure.

Therefore, the individualization of the dosage of GCV, can contribute greatly to achieve optimal exposure to the drug in transplant patients, especially in the cases of extreme values of renal function (CrCl decreased and high). As a consequence, minimize adverse effects, ensure greater efficiency in the target population and reduce associated costs.

Eligibility criteria: Inclusion Criteria:

* Subjects must be 18 or older, weigh more than 34kg and may be of either sex and race.
* Subjects must be willing to give informed consent (IC) in writing and be able to do and follow the study. If a subject cannot give informed consent in writing , a legal representative could sign in his place.
* Women of childbearing potential should perform a pregnancy test at the time of entry and accept the use of a medically acceptable contraceptive method during the study.

Exclusion Criteria:

* Creatinine Clearance (CrCl )\<10 mL / min.
* Subjects may not have a history of type I hypersensitivity or idiosyncratic reactions to drugs ganciclovir/valganciclovir
* Pregnancy women.
* Women breast feeding
* Subjects may not present at time of inclusion any clinically significant disease that could interfere with study evaluations.
* Previous participation in another clinical trial sponsored by pharmaceutical industry, in which the promoter and the protocol set which should be the treatment for CMV.

Primary outcomes:
measure: Area under the concentration time curve (AUC)of ganciclovir in steady state
timeFrame: Change from baseline to the end of the treatment, with an expected average of treatment of 4 weeks in treatment and 90 days in prophylaxis patients.
Secondary outcomes:
measure: CMV viral load measured by quantitative polymerase chain reaction (PCR)
timeFrame: Change from baseline to day 30 of study entry
measure: CMV viral load measured by quantitative polymerase chain reaction (PCR)
timeFrame: Change from baseline to day 60 of study entry
measure: CMV viral load measured by quantitative polymerase chain reaction (PCR)
timeFrame: Change from baseline to day 90 of study entry
measure: T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
timeFrame: Change from day 40 of treatment to day 20 after end of treatment.
measure: T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)
timeFrame: Change from baseline to day 20 of treatment
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Nephrology Department- Hospital Universitari Bellvtge
state: Barcelona
Study officials:
affiliation: Nephrology Department-Hospital Universitari Bellvitge
name: Nuria Lloberas, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Padulles A, Colom H, Bestard O, Melilli E, Sabe N, Rigo R, Niubo J, Torras J, Llado L, Manito N, Caldes A, Cruzado JM, Grinyo JM, Lloberas N. Contribution of Population Pharmacokinetics to Dose Optimization of Ganciclovir-Valganciclovir in Solid-Organ Transplant Patients. Antimicrob Agents Chemother. 2016 Mar 25;60(4):1992-2002. doi: 10.1128/AAC.02130-15. Print 2016 Apr.